Purinergic Signalling

, Volume 9, Issue 4, pp 491–540 | Cite as

Purinergic signalling and cancer

  • Geoffrey BurnstockEmail author
  • Francesco Di Virgilio
Review Article


Receptors for extracellular nucleotides are widely expressed by mammalian cells. They mediate a large array of responses ranging from growth stimulation to apoptosis, from chemotaxis to cell differentiation and from nociception to cytokine release, as well as neurotransmission. Pharma industry is involved in the development and clinical testing of drugs selectively targeting the different P1 nucleoside and P2 nucleotide receptor subtypes. As described in detail in the present review, P2 receptors are expressed by all tumours, in some cases to a very high level. Activation or inhibition of selected P2 receptor subtypes brings about cancer cell death or growth inhibition. The field has been largely neglected by current research in oncology, yet the evidence presented in this review, most of which is based on in vitro studies, although with a limited amount from in vivo experiments and human studies, warrants further efforts to explore the therapeutic potential of purinoceptor targeting in cancer.


P2 receptors Extracellular ATP Cell growth Apoptosis Cancer Anti-cancer drugs 


  1. 1.
    Burnstock G (1972) Purinergic nerves. Pharmacol Rev 24:509–581PubMedGoogle Scholar
  2. 2.
    Ralevic V, Burnstock G (1998) Receptors for purines and pyrimidines. Pharmacol Rev 50:413–492PubMedGoogle Scholar
  3. 3.
    Burnstock G (2007) Purine and pyrimidine receptors. Cell and Mol Life Sci 64:1471–1483Google Scholar
  4. 4.
    Burnstock G, Knight GE (2004) Cellular distribution and functions of P2 receptor subtypes in different systems. Int Rev Cytol 240:31–304PubMedGoogle Scholar
  5. 5.
    Burnstock G (2006) Pathophysiology and therapeutic potential of purinergic signaling. Pharmacol Rev 58:58–86PubMedGoogle Scholar
  6. 6.
    Burnstock G (2007) Physiology and pathophysiology of purinergic neurotransmission. Physiol Rev 87:659–797PubMedGoogle Scholar
  7. 7.
    Fishman P, Bar-Yehuda S, Madi L, Cohn I (2002) A3 adenosine receptor as a target for cancer therapy. Anticancer Drugs 13:437–443PubMedGoogle Scholar
  8. 8.
    Abraham EH, Salikhova AY, Rapaport E (2003) ATP in the treatment of advanced cancer. Curr Top Membr 54:415–452Google Scholar
  9. 9.
    Merighi S, Mirandola P, Varani K, Gessi S, Leung E, Baraldi PG, Tabrizi MA, Borea PA (2003) A glance at adenosine receptors: novel target for antitumor therapy. Pharmacol Ther 100:31–48PubMedGoogle Scholar
  10. 10.
    White N, Burnstock G (2006) P2 receptors and cancer. Trends Pharmacol Sci 27:211–217PubMedGoogle Scholar
  11. 11.
    Deli T, Csernoch L (2008) Extracellular ATP and cancer: an overview with special reference to P2 purinergic receptors. Pathol Oncol Res 14:219–231PubMedGoogle Scholar
  12. 12.
    Pathak R, Bhatnagar S, Dubey AK (2008) Mechanisms underlying the opposing effects of P2Y receptors on the cell cycle. J Recept Signal Transduct Res 28:505–529PubMedGoogle Scholar
  13. 13.
    Shabbir M, Burnstock G (2009) Purinergic receptor-mediated effects of adenosine 5′-triphosphate in urological malignant diseases. Int J Urol 16:143–150PubMedGoogle Scholar
  14. 14.
    Di Virgilio F, Ferrari D, Adinolfi E (2009) P2X7: a growth-promoting receptor—implications for cancer. Purinergic Signal 5:251–256PubMedPubMedCentralGoogle Scholar
  15. 15.
    Stagg J, Smyth MJ (2010) Extracellular adenosine triphosphate and adenosine in cancer. Oncogene 29:5346–5358PubMedGoogle Scholar
  16. 16.
    Gessi S, Merighi S, Sacchetto V, Simioni C, Borea PA (2011) Adenosine receptors and cancer. Biochim Biophys Acta 1808:1400–1412PubMedGoogle Scholar
  17. 17.
    Di Virgilio F (2012) Purines, purinergic receptors, and cancer. Cancer Res 72:5441–5447PubMedGoogle Scholar
  18. 18.
    Rapaport E (1983) Treatment of human tumor cells with ADP or ATP yields arrest of growth in the S phase of the cell cycle. J Cell Physiol 114:279–283PubMedGoogle Scholar
  19. 19.
    Rapaport E (1988) Experimental cancer therapy in mice by adenine nucleotides. Eur J Cancer Clin Oncol 24:1491–1497PubMedGoogle Scholar
  20. 20.
    Rapaport E (1990) Mechanisms of anticancer activities of adenine nucleotides in tumor-bearing hosts. Ann N Y Acad Sci 603:142–149PubMedGoogle Scholar
  21. 21.
    Rapaport E, Fontaine J (1989) Anticancer activities of adenine nucleotides in mice are mediated through expansion of erythrocyte ATP pools. Proc Natl Acad Sci USA 86:1662–1666PubMedPubMedCentralGoogle Scholar
  22. 22.
    Spychala J (2000) Tumor-promoting functions of adenosine. Pharmacol Ther 87:161–173PubMedGoogle Scholar
  23. 23.
    Hoepfner M, Kap H, Jansen A, Lemmer K, Hanski C, Riecken EO, Scheruebl H (1999) Extracellular ATP induces apoptosis and inhibits growth of colorectal carcinomas. Gastroenterology 116:A423Google Scholar
  24. 24.
    Chahwala SB, Cantley LC (1984) Extracellular ATP induces ion fluxes and inhibits growth of Friend erythroleukemia cells. J Biol Chem 259:13717–13722PubMedGoogle Scholar
  25. 25.
    Seetulsingh-Goorah SP, Stewart BW (1998) Growth inhibition of HL-60 cells by extracellular ATP: concentration-dependent involvement of a P2 receptor and adenosine generation. Biochem Biophys Res Commun 250:390–396PubMedGoogle Scholar
  26. 26.
    Maaser K, Höpfner M, Kap H, Sutter AP, Barthel B, von Lampe B, Zeitz M, Scherübl H (2002) Extracellular nucleotides inhibit growth of human oesophageal cancer cells via P2Y2-receptors. Br J Cancer 86:636–644PubMedPubMedCentralGoogle Scholar
  27. 27.
    Dubyak GR, De Young MB (1985) Intracellular Ca2+ mobilization activated by extracellular ATP in Ehrlich ascites tumor cells. J Biol Chem 260:10653–10661PubMedGoogle Scholar
  28. 28.
    Greig AVH, Linge C, Healy V, Lim P, Clayton E, Rustin MH, McGrouther DA, Burnstock G (2003) Expression of purinergic receptors in non-melanoma skin cancers and their functional roles in A431 cells. J Invest Dermatol 121:315–327PubMedGoogle Scholar
  29. 29.
    Schäfer R, Sedehizade F, Welte T, Reiser G (2003) ATP- and UTP-activated P2Y receptors differently regulate proliferation of human lung epithelial tumor cells. Am J Physiol Lung Cell Mol Physiol 285:L376–L385PubMedGoogle Scholar
  30. 30.
    Wang Q, Wang L, Feng YH, Li X, Zeng R, Gorodeski GI (2004) P2X7 receptor-mediated apoptosis of human cervical epithelial cells. Am J Physiol Cell Physiol 287:C1349–C1358PubMedGoogle Scholar
  31. 31.
    Horstman DA, Tennes KA, Putney JW Jr (1986) ATP-induced calcium mobilization and inositol 1,4,5-triphosphate formation in H-35 hepatoma cells. FEBS Lett 204:189–192PubMedGoogle Scholar
  32. 32.
    Shabbir M, Thompson CS, Jarmulowicz M, Mikhailidis DP, Burnstock G (2008) Effect of extracellular ATP on the growth of hormone refractory prostate cancer in vivo. BJU Int 102:108–112PubMedGoogle Scholar
  33. 33.
    Shabbir M, Ryten M, Thompson CS, Mikhailidis DP, Burnstock G (2008) Purinergic receptor-mediated effects of ATP in high-grade bladder cancer. BJU Int 101:106–112PubMedGoogle Scholar
  34. 34.
    Kim NH, Park KS, Sohn JH, Yeh BI, Ko CM, Kong ID (2011) Functional expression of P2Y receptors in WERI-Rb1 retinoblastoma cells. Korean J Physiol Pharmacol 15:61–66PubMedPubMedCentralGoogle Scholar
  35. 35.
    Gómez-Villafuertes R, del Puerto A, Díaz-Hernández M, Bustillo D, Díaz-Hernández JI, Huerta PG, Artalejo AR, Garrido JJ, Miras-Portugal MT (2009) Ca2+/calmodulin-dependent kinase II signalling cascade mediates P2X7 receptor-dependent inhibition of neuritogenesis in neuroblastoma cells. FEBS J 276:5307–5325PubMedGoogle Scholar
  36. 36.
    Suplat-Wypych D, Dygas A, Barañska J (2010) 2′,3′-O-(4-benzoylbenzoyl)-ATP-mediated calcium signaling in rat glioma C6 cells: role of the P2Y2 nucleotide receptor. Purinergic Signalling 6:317–325PubMedPubMedCentralGoogle Scholar
  37. 37.
    White N, Butler PEM, Burnstock G (2005) Human melanomas express functional P2X7 receptors. Cell Tissue Res 321:411–418PubMedGoogle Scholar
  38. 38.
    White N, Knight GE, Butler PEM, Burnstock G (2009) An in vivo model of melanoma: treatment with ATP. Purinergic Signalling 5:327–333PubMedPubMedCentralGoogle Scholar
  39. 39.
    Ahmann FR, Garewal HS, Schifman R, Celniker A, Rodney S (1987) Intracellular adenosine triphosphate as a measure of human tumor cell viability and drug modulated growth. In Vitro Cell Dev Biol 23:474–480PubMedGoogle Scholar
  40. 40.
    Maehara Y, Kusumoto H, Anai H, Kusumoto T, Sugimachi K (1987) Human tumor tissues have higher ATP contents than normal tissues. Clin Chim Acta 169:341–343PubMedGoogle Scholar
  41. 41.
    Martins JP, Silva RB, Coutinho-Silva R, Takiya CM, Battastini AM, Morrone FB, Campos MM (2012) P2X7 purinergic receptor and its role in inflammatory and nociceptive alterations associated to cyclophosphamide-induced hemorrhagic cystitis in mice. Br J Pharmacol 165:183–196PubMedPubMedCentralGoogle Scholar
  42. 42.
    Yegutkin GG, Marttila-Ichihara F, Karikoski M, Niemela J, Laurila JP, Elima K, Jalkanen S, Salmi M (2011) Altered purinergic signaling in CD73-deficient mice inhibits tumor progression. Eur J Immunol 41:1231–1241PubMedGoogle Scholar
  43. 43.
    Feng L, Sun X, Csizmadia E, Han L, Bian S, Murakami T, Wang X, Robson SC, Wu Y (2011) Vascular CD39/ENTPD1 directly promotes tumor cell growth by scavenging extracellular adenosine triphosphate. Neoplasia 13:206–216PubMedPubMedCentralGoogle Scholar
  44. 44.
    Tada Y, Yokomizo A, Shiota M, Song Y, Kashiwagi E, Kuroiwa K, Oda Y, Naito S (2011) Ectonucleoside triphosphate diphosphohydrolase 6 expression in testis and testicular cancer and its implication in cisplatin resistance. Oncol Rep 26:161–167PubMedGoogle Scholar
  45. 45.
    White N, Ryten M, Clayton E, Butler P, Burnstock G (2005) P2Y purinergic receptors regulate the growth of human melanomas. Cancer Lett 224:81–91PubMedGoogle Scholar
  46. 46.
    Yuahasi KK, Demasi MA, Tamajusuku AS, Lenz G, Sogayar MC, Fornazari M, Lameu C, Nascimento IC, Glaser T, Schwindt TT, Negraes PD, Ulrich H (2012) Regulation of neurogenesis and gliogenesis of retinoic acid-induced P19 embryonal carcinoma cells by P2X2 and P2X7 receptors studied by RNA interference. Int J Dev Neurosci 30:91–97PubMedGoogle Scholar
  47. 47.
    Gorodeski GI (2009) P2X7-mediated chemoprevention of epithelial cancers. Expert Opin Ther Targets 13:1313–1332PubMedGoogle Scholar
  48. 48.
    Zanovello P, Bronte V, Rosato A, Pizzo P, Di Virgilio F (1990) Responses of mouse lymphocytes to extracellular ATP. II. Extracellular ATP causes cell type-dependent lysis and DNA fragmentation. J Immunol 145:1545–1550PubMedGoogle Scholar
  49. 49.
    Pizzo P, Murgia M, Zambon A, Zanovello P, Bronte V, Pietrobon D, Di Virgilio F (1992) Role of P2z purinergic receptors in ATP-mediated killing of tumor necrosis factor (TNF)-sensitive and TNF-resistant L929 fibroblasts. J Immunol 149:3372–3378PubMedGoogle Scholar
  50. 50.
    Adinolfi E, Callegari MG, Ferrari D, Bolognesi C, Minelli M, Wieckowski MR, Pinton P, Rizzuto R, Di Virgilio F (2005) Basal activation of the P2X7 ATP receptor elevates mitochondrial calcium and potential, increases cellular ATP levels, and promotes serum-independent growth. Mol Biol Cell 16:3260–3272PubMedPubMedCentralGoogle Scholar
  51. 51.
    Thompson BA, Storm MP, Hewinson J, Hogg S, Welham MJ, Mackenzie AB (2012) A novel role for P2X7 receptor signalling in the survival of mouse embryonic stem cells. Cell Signal 24:770–778PubMedPubMedCentralGoogle Scholar
  52. 52.
    Adinolfi E, Callegari MG, Cirillo M, Pinton P, Giorgi C, Cavagna D, Rizzuto R, Di Virgilio F (2009) Expression of the P2X7 receptor increases the Ca2+ content of the endoplasmic reticulum, activates NFATc1, and protects from apoptosis. J Biol Chem 284:10120–10128PubMedPubMedCentralGoogle Scholar
  53. 53.
    Adinolfi E, Cirillo M, Woltersdorf R, Falzoni S, Chiozzi P, Pellegatti P, Callegari MG, Sandona D, Markwardt F, Schmalzing G, Di Virgilio F (2010) Trophic activity of a naturally occurring truncated isoform of the P2X7 receptor. FASEB J 24:3393–3404PubMedGoogle Scholar
  54. 54.
    Jelassi B, Chantôme A, Alcaraz-Pérez F, Baroja-Mazo A, Cayuela ML, Pelegrin P, Surprenant A, Roger S (2011) P2X7 receptor activation enhances SK3 channels- and cystein cathepsin-dependent cancer cells invasiveness. Oncogene 30:2108–2122PubMedGoogle Scholar
  55. 55.
    Li X, Qi X, Zhou L, Fu W, Abdul-Karim FW, Maclennan G, Gorodeski GI (2009) P2X7 receptor expression is decreased in epithelial cancer cells of ectodermal, uro-genital sinus, and distal paramesonephric duct origin. Purinergic Signal 5:351–368PubMedPubMedCentralGoogle Scholar
  56. 56.
    Feng YH, Li X, Zeng R, Gorodeski GI (2006) Endogenously expressed truncated P2X7 receptor lacking the C-terminus is preferentially upregulated in epithelial cancer cells and fails to mediate ligand-induced pore formation and apoptosis. Nucleosides Nucleotides Nucleic Acids 25:1271–1276PubMedGoogle Scholar
  57. 57.
    van der Weyden L, Conigrave AD, Morris MB (2000) Signal transduction and white cell maturation via extracellular ATP and the P2Y11 receptor. Immunol Cell Biol 78:369–374PubMedGoogle Scholar
  58. 58.
    Greig AVH, Linge C, Terenghi G, McGrouther DA, Burnstock G (2003) Purinergic receptors are part of a functional signalling system for proliferation and differentiation of human epidermal keratinocytes. J Invest Dermatol 120:1007–1015PubMedGoogle Scholar
  59. 59.
    Li S, Huang S, Peng SB (2005) Overexpression of G protein-coupled receptors in cancer cells: involvement in tumor progression. Int J Oncol 27:1329–1339PubMedGoogle Scholar
  60. 60.
    Madi L, Ochaion A, Rath-Wolfson L, Bar-Yehuda S, Erlanger A, Ohana G, Harish A, Merimski O, Barer F, Fishman P (2004) The A3 adenosine receptor is highly expressed in tumor versus normal cells: potential target for tumor growth inhibition. Clin Cancer Res 10:4472–4479PubMedGoogle Scholar
  61. 61.
    Placzek WJ, Almeida MS, Wüuthrich K (2007) NMR structure and functional characterization of a human cancer-related nucleoside triphosphatase. J Mol Biol 367:788–801PubMedGoogle Scholar
  62. 62.
    Kalhan A, Gharibi B, Vazquez M, Jasani B, Neal J, Kidd M, Modlin IM, Pfragner R, Rees DA, Ham J (2012) Adenosine A2A and A2B receptor expression in neuroendocrine tumours: potential targets for therapy. Purinergic Signal 8:265–274PubMedPubMedCentralGoogle Scholar
  63. 63.
    Ohta A, Gorelik E, Prasad SJ, Ronchese F, Lukashev D, Wong MK, Huang X, Caldwell S, Liu K, Smith P, Chen JF, Jackson EK, Apasov S, Abrams S, Sitkovsky M (2006) A2A adenosine receptor protects tumors from antitumor T cells. Proc Natl Acad Sci U S A 103:13132–13137PubMedPubMedCentralGoogle Scholar
  64. 64.
    Hoskin DW, Reynolds T, Blay J (1994) Adenosine as a possible inhibitor of killer T-cell activation in the microenvironment of solid tumours. Int J Cancer 59:854–855PubMedGoogle Scholar
  65. 65.
    Pellegatti P, Raffaghello L, Bianchi G, Piccardi F, Pistoia V, Di Virgilio F (2008) Increased level of extracellular ATP at tumor sites: in vivo imaging with plasma membrane luciferase. PLoS One 3:e2599PubMedPubMedCentralGoogle Scholar
  66. 66.
    Wilhelm K, Ganesan J, Muller T, Durr C, Grimm M, Beilhack A, Krempl CD, Sorichter S, Gerlach UV, Juttner E, Zerweck A, Gartner F, Pellegatti P, Di Virgilio F, Ferrari D, Kambham N, Fisch P, Finke J, Idzko M, Zeiser R (2010) Graft-versus-host disease is enhanced by extracellular ATP activating P2X7R. Nat Med 16:1434–1438PubMedGoogle Scholar
  67. 67.
    Phillis JW, Wu PH (1981) Adenosine may regulate the vascular supply and thus the growth and spread of neoplastic tissues: a proposal. Gen Pharmacol 12:309–310PubMedGoogle Scholar
  68. 68.
    Mitchell BS, Schumacher U, Stauber VV, Kaiserling E (1994) Are breast tumours innervated? Immunohistological investigations using antibodies against the neuronal marker protein gene product 9.5 (PGP 9.5) in benign and malignant breast lesions. Eur J Cancer 30A:1100–1103PubMedGoogle Scholar
  69. 69.
    Ashraf S, Crowe R, Loizidou MC, Turmaine M, Taylor I, Burnstock G (1996) The absence of autonomic perivascular nerves in human colorectal liver metastases. Br J Cancer 73:349–359PubMedPubMedCentralGoogle Scholar
  70. 70.
    Ashraf S, Loizidou M, Crowe R, Turmaine M, Taylor I, Burnstock G (1997) Blood vessels in liver metastases from both sarcoma and carcinoma lack perivascular innervation and smooth muscle cells. Clin Exp Metastasis 15:484–498PubMedGoogle Scholar
  71. 71.
    Chamary VL, Robson T, Loizidou M, Boulos PB, Burnstock G (2000) Progressive loss of perivascular nerves adjacent to colorectal cancer. Eur J Surg Oncol 26:588–593PubMedGoogle Scholar
  72. 72.
    Gil M, Skopinska-Rózewska E, Radomska D, Demkow U, Skurzak H, Rochowska M, Beuth J, Roszkowski K (1993) Effect of purinergic receptor antagonists suramin and theobromine on tumor-induced angiogenesis in BALB/c mice. Folia Biol (Praha) 39:63–68Google Scholar
  73. 73.
    Komi Y, Ohno O, Suzuki Y, Shimamura M, Shimokado K, Umezawa K, Kojima S (2007) Inhibition of tumor angiogenesis by targeting endothelial surface ATP synthase with sangivamycin. Jpn J Clin Oncol 37:867–873PubMedGoogle Scholar
  74. 74.
    Nejime N, Tanaka N, Yoshihara R, Kagota S, Yoshikawa N, Nakamura K, Kunitomo M, Hashimoto M, Shinozuka K (2008) Effect of P2 receptor on the intracellular calcium increase by cancer cells in human umbilical vein endothelial cells. Naunyn Schmiedebergs Arch Pharmacol 377:429–436PubMedGoogle Scholar
  75. 75.
    Hazama A, Fan HT, Abdullaev I, Maeno E, Tanaka S, Ando-Akatsuka Y, Okada Y (2000) Swelling-activated, cystic fibrosis transmembrane conductance regulator-augmented ATP release and Cl conductances in murine C127 cells. J Physiol 523 Pt 1:1–11PubMedGoogle Scholar
  76. 76.
    Boyd Tressler A, Dubyak G (2012) Multiple mechanisms for ATP release from apoptotic tumour cells. J Immunol 188:46.21Google Scholar
  77. 77.
    Martin DS, Bertino JR, Koutcher JA (2000) ATP depletion + pyrimidine depletion can markedly enhance cancer therapy: fresh insight for a new approach. Cancer Res 60:6776–6783PubMedGoogle Scholar
  78. 78.
    Martin DS, Spriggs D, Koutcher JA (2001) A concomitant ATP-depleting strategy markedly enhances anticancer agent activity. Apoptosis 6:125–131PubMedGoogle Scholar
  79. 79.
    Lukashev D, Sitkovsky M, Ohta A (2007) From "Hellstrom Paradox" to anti-adenosinergic cancer immunotherapy. Purinergic Signal 3:129–134PubMedPubMedCentralGoogle Scholar
  80. 80.
    Sitkovsky M, Lukashev D, Deaglio S, Dwyer K, Robson SC, Ohta A (2008) Adenosine A2A receptor antagonists: blockade of adenosinergic effects and T regulatory cells. Br J Pharmacol 153(Suppl 1):S457–S464PubMedPubMedCentralGoogle Scholar
  81. 81.
    Martins I, Tesniere A, Kepp O, Michaud M, Schlemmer F, Senovilla L, Séror C, Métivier D, Perfettini JL, Zitvogel L, Kroemer G (2009) Chemotherapy induces ATP release from tumor cells. Cell Cycle 8:3723–3728PubMedGoogle Scholar
  82. 82.
    Ghiringhelli F, Apetoh L, Tesniere A, Aymeric L, Ma Y, Ortiz C, Vermaelen K, Panaretakis T, Mignot G, Ullrich E, Perfettini JL, Schlemmer F, Tasdemir E, Uhl M, Genin P, Civas A, Ryffel B, Kanellopoulos J, Tschopp J, Andre F, Lidereau R, McLaughlin NM, Haynes NM, Smyth MJ, Kroemer G, Zitvogel L (2009) Activation of the NLRP3 inflammasome in dendritic cells induces IL-1beta-dependent adaptive immunity against tumors. Nat Med 15:1170–1178PubMedGoogle Scholar
  83. 83.
    Aymeric L, Apetoh L, Ghiringhelli F, Tesniere A, Martins I, Kroemer G, Smyth MJ, Zitvogel L (2010) Tumor cell death and ATP release prime dendritic cells and efficient anticancer immunity. Cancer Res 70:855–858PubMedGoogle Scholar
  84. 84.
    Marteau F, Gonzalez NS, Communi D, Goldman M, Boeynaems JM, Communi D (2005) Thrombospondin-1 and indoleamine 2,3-dioxygenase are major targets of extracellular ATP in human dendritic cells. Blood 106:3860–3866PubMedGoogle Scholar
  85. 85.
    Michaud M, Martins I, Sukkurwala AQ, Adjemian S, Ma Y, Pellegatti P, Shen S, Kepp O, Scoazec M, Mignot G, Rello-Varona S, Tailler M, Menger L, Vacchelli E, Galluzzi L, Ghiringhelli F, Di Virgilio F, Zitvogel L, Kroemer G (2011) Autophagy-dependent anticancer immune responses induced by chemotherapeutic agents in mice. Science 334:1573–1577PubMedGoogle Scholar
  86. 86.
    Haskell CM, Wong M, Williams A, Lee LY (1996) Phase I trial of extracellular adenosine 5′-triphosphate in patients with advanced cancer. Med Pediatr Oncol 27:165–173PubMedGoogle Scholar
  87. 87.
    Haskell CM, Mendoza E, Pisters KM, Fossella FV, Figlin RA (1998) Phase II study of intravenous adenosine 5′-triphosphate in patients with previously untreated stage IIIB and stage IV non-small cell lung cancer. Invest New Drugs 16:81–85PubMedGoogle Scholar
  88. 88.
    Agteresch HJ, Dagnelie PC, Rietveld T, van den Berg JW, Danser AH, Wilson JH (2000) Pharmacokinetics of intravenous ATP in cancer patients. Eur J Clin Pharmacol 56:49–55PubMedGoogle Scholar
  89. 89.
    Agteresch HJ, Rietveld T, Kerkhofs LG, van den Berg JW, Wilson JH, Dagnelie PC (2002) Beneficial effects of adenosine triphosphate on nutritional status in advanced lung cancer patients: a randomized clinical trial. J Clin Oncol 20:371–378PubMedGoogle Scholar
  90. 90.
    Chahrour O, Cairns D, Omran Z (2012) Small molecule kinase inhibitors as anti-cancer therapeutics. Mini Rev Med Chem 12:399–411PubMedGoogle Scholar
  91. 91.
    Agteresch HJ, Leij-Halfwerk S, van den Berg JW, Hordijk-Luijk CH, Wilson JH, Dagnelie PC (2000) Effects of ATP infusion on glucose turnover and gluconeogenesis in patients with advanced non-small-cell lung cancer. Clin Sci (Lond) 98:689–695Google Scholar
  92. 92.
    Rapaport E, Fontaine J (1989) Generation of extracellular ATP in blood and its mediated inhibition of host weight loss in tumor-bearing mice. Biochem Pharmacol 38:4261–4266PubMedGoogle Scholar
  93. 93.
    Agteresch HJ, van Rooijen MHC, van den Berg JWO, Minderman-Voortman GJ, Wilson JHP, Dagnelie PC (2003) Growth inhibition of lung cancer cells by adenosine 5′-triphosphate. Drug Dev Res 60:196–203Google Scholar
  94. 94.
    Arts ICW, Swennen ELR, Vandeurzen KGA, Dagnelie PC (2008) Effect of ATP on survival, tumour response, nutritional status and quality of life in lung cancer patients: a multicentre, double-blind randomized trial. Purinergic Signalling 4:S194–S195Google Scholar
  95. 95.
    Beijer S, Gielisse EA, Hupperets PS, van den Borne BE, van den Beuken-van EM, Nijziel MR, van Henten AM, Dagnelie PC (2007) Intravenous ATP infusions can be safely administered in the home setting: a study in pre-terminal cancer patients. Invest New Drugs 25:571–579PubMedPubMedCentralGoogle Scholar
  96. 96.
    Beijer S, Wijckmans NE, van Rossum E, Spreeuwenberg C, Winkens RA, Ars L, Dagnelie PC (2008) Treatment adherence and patients’ acceptance of home infusions with adenosine 5′-triphosphate (ATP) in palliative home care. Support Care Cancer 16:1419–1424PubMedGoogle Scholar
  97. 97.
    Beijer S, Hupperets PS, van den Borne BE, Eussen SR, van Henten AM, van den Beuken-van EM, de Graeff A, Ambergen TA, van den Brandt PA, Dagnelie PC (2009) Effect of adenosine 5′-triphosphate infusions on the nutritional status and survival of preterminal cancer patients. Anticancer Drugs 20:625–633PubMedGoogle Scholar
  98. 98.
    Swennen EL, Dagnelie PC, Van den Beucken T, Bast A (2008) Radioprotective effects of ATP in human blood ex vivo. Biochem Biophys Res Commun 367:383–387PubMedGoogle Scholar
  99. 99.
    Ohshima Y, Tsukimoto M, Takenouchi T, Harada H, Suzuki A, Sato M, Kitani H, Kojima S (2010) γ-Irradiation induces P2X7 receptor-dependent ATP release from B16 melanoma cells. Biochim Biophys Acta 1800:40–46PubMedGoogle Scholar
  100. 100.
    Ohshima Y, Tsukimoto M, Harada H, Kojima S (2012) Involvement of connexin43 hemichannel in ATP release after γ-irradiation. J Radiat Res 53:551–557PubMedPubMedCentralGoogle Scholar
  101. 101.
    Mancuso M, Pasquali E, Leonardi S, Rebessi S, Tanori M, Giardullo P, Borra F, Pazzaglia S, Naus CC, Di Majo V, Saran A (2011) Role of connexin43 and ATP in long-range bystander radiation damage and oncogenesis in vivo. Oncogene 30:4601–4608PubMedGoogle Scholar
  102. 102.
    Nishimaki N, Tsukimoto M, Kitami A, Kojima S (2012) Autocrine regulation of γ-irradiation-induced DNA damage response via extracellular nucleotides-mediated activation of P2Y6 and P2Y12 receptors. DNA Repair (Amst) 11:657–665Google Scholar
  103. 103.
    Spungin B, Friedberg I (1993) Growth inhibition of breast cancer cells induced by exogenous ATP. J Cell Physiol 157:502–508PubMedGoogle Scholar
  104. 104.
    Colofiore JR, Stolfi RL, Nord LD, Martin DS (1995) On the relationship of ATP depletion to chemotherapeutically-induced tumor regression. Int J Oncol 7:1401–1404PubMedGoogle Scholar
  105. 105.
    Flezar M, Heisler S (1993) P2-purinergic receptors in human breast tumor cells: coupling of intracellular calcium signaling to anion secretion. J Pharmacol Exp Ther 265:1499–1510PubMedGoogle Scholar
  106. 106.
    Dixon CJ, Bowler WB, Fleetwood P, Ginty AF, Gallagher JA, Carron JA (1997) Extracellular nucleotides stimulate proliferation in MCF-7 breast cancer cells via P2-purinoceptors. Br J Cancer 75:34–39PubMedPubMedCentralGoogle Scholar
  107. 107.
    Wagstaff SC, Bowler WB, Gallagher JA, Hipskind RA (2000) Extracellular ATP activates multiple signalling pathways and potentiates growth factor-induced c-fos gene expression in MCF-7 breast cancer cells. Carcinogenesis 21:2175–2181PubMedGoogle Scholar
  108. 108.
    Li HJ, Wang LY, Qu HN, Yu LH, Burnstock G, Ni X, Xu M, Ma B (2011) P2Y2 receptor-mediated modulation of estrogen-induced proliferation of breast cancer cells. Mol Cell Endocrinol 338:28–37PubMedGoogle Scholar
  109. 109.
    Spychala J, Lazarowski E, Ostapkowicz A, Ayscue LH, Jin A, Mitchell BS (2004) Role of estrogen receptor in the regulation of ecto-5′-nucleotidase and adenosine in breast cancer. Clin Cancer Res 10:708–717PubMedGoogle Scholar
  110. 110.
    do Carmo Araujo M, Rocha JB, Morsch A, Zanin R, Bauchspiess R, Morsch VM, Schetinger MR (2005) Enzymes that hydrolyze adenine nucleotides in platelets from breast cancer patients. Biochim Biophys Acta 1740:421–426PubMedGoogle Scholar
  111. 111.
    Seyedabadi M, Ghahremani MH, Ostad SN (2009) ATP depletion as a consequence of hypoxia enhances tamoxifen antiproliferative effects in T47D breast carcinoma cells. Oncol Res 18:221–228PubMedGoogle Scholar
  112. 112.
    Dohán O, De la Vieja A, Carrasco N (2006) Hydrocortisone and purinergic signaling stimulate sodium/iodide symporter (NIS)-mediated iodide transport in breast cancer cells. Mol Endocrinol 20:1121–1137PubMedGoogle Scholar
  113. 113.
    Wang Z (2004) Roles of K+ channels in regulating tumour cell proliferation and apoptosis. Pflugers Arch 448:274–286PubMedGoogle Scholar
  114. 114.
    Gow IF, Thomson J, Davidson J, Shennan DB (2005) The effect of a hyposmotic shock and purinergic agonists on K+(Rb+) efflux from cultured human breast cancer cells. Biochim Biophys Acta 1712:52–61PubMedGoogle Scholar
  115. 115.
    Yu SP (2003) Regulation and critical role of potassium homeostasis in apoptosis. Prog Neurobiol 70:363–386PubMedGoogle Scholar
  116. 116.
    Loo WT, Tong JM, Cheung MN, Chow LW (2006) A new predictive and prognostic marker (ATP bioluminescence and positron emission tomography) in vivo and in vitro for delivering adjuvant treatment plan to invasive breast tumor patients. Biomed Pharmacother 60:285–288PubMedGoogle Scholar
  117. 117.
    Pan J, Sun LC, Tao YF, Zhou Z, Du XL, Peng L, Feng X, Wang J, Li YP, Liu L, Wu SY, Zhang YL, Hu SY, Zhao WL, Zhu XM, Lou GL, Ni J (2011) ATP synthase ecto-α-subunit: a novel therapeutic target for breast cancer. J Transl Med 9:211PubMedPubMedCentralGoogle Scholar
  118. 118.
    Kim HA, Yom CK, Moon BI, Choe KJ, Sung SH, Han WS, Choi HY, Kim HK, Park HK, Choi SH, Yoon EJ, Oh SY (2008) The use of an in vitro adenosine triphosphate-based chemotherapy response assay to predict chemotherapeutic response in breast cancer. Breast 17:19–26PubMedGoogle Scholar
  119. 119.
    Koo JS, Jung W, Shin E, Lee HD, Jeong J, Kim KH, Jeong H, Hong SW (2009) Impact of grade, hormone receptor, and HER-2 status in women with breast cancer on response to specific chemotherapeutic agents by in vitro adenosine triphosphate-based chemotherapy response assay. J Korean Med Sci 24:1150–1157PubMedPubMedCentralGoogle Scholar
  120. 120.
    Qi CJ, Ning YL, Zhu YL, Min HY, Ye H, Qian KQ (2009) In vitro chemosensitivity in breast cancer using ATP-tumor chemosensitivity assay. Arch Pharm Res 32:1737–1742PubMedGoogle Scholar
  121. 121.
    Buffon A, Ribeiro VB, Wink MR, Casali EA, Sarkis JJ (2007) Nucleotide metabolizing ecto-enzymes in Walker 256 tumor cells: molecular identification, kinetic characterization and biochemical properties. Life Sci 80:950–958PubMedGoogle Scholar
  122. 122.
    Buffon A, Wink MR, Ribeiro BV, Casali EA, Libermann TA, Zerbini LF, Robson SC, Sarkis JJ (2007) NTPDase and 5′ ecto-nucleotidase expression profiles and the pattern of extracellular ATP metabolism in the Walker 256 tumor. Biochim Biophys Acta 1770:1259–1265PubMedGoogle Scholar
  123. 123.
    Buffon A, Casali EA, Cardoso VV, Zerbini LF, Robson SC, Sarkis JJ, Wink MR (2010) Differential expression of nucleotide pyrophosphatase/phosphodiesterases by Walker 256 mammary cancer cells in solid tumors and malignant ascites. Life Sci 86:435–440PubMedGoogle Scholar
  124. 124.
    Rumjahn SM, Javed MA, Wong N, Law WE, Buxton IL (2007) Purinergic regulation of angiogenesis by human breast carcinoma-secreted nucleoside diphosphate kinase. Br J Cancer 97:1372–1380PubMedPubMedCentralGoogle Scholar
  125. 125.
    Yokdang N, Tellez JD, Tian H, Norvell J, Barsky SH, Valencik M, Buxton IL (2011) A role for nucleotides in support of breast cancer angiogenesis: heterologous receptor signalling. Br J Cancer 104:1628–1640PubMedPubMedCentralGoogle Scholar
  126. 126.
    Scodelaro Bilbao P, Boland R, Russo de Boland A, Santillán G (2007) ATP modulation of mitogen activated protein kinases and intracellular Ca2+ in breast cancer (MCF-7) cells. Arch Biochem Biophys 466:15–23PubMedGoogle Scholar
  127. 127.
    Scodelaro Bilbao P, Boland R, Santillán G (2010) ATP modulates transcription factors through P2Y2 and P2Y4 receptors via PKC/MAPKs and PKC/Src pathways in MCF-7 cells. Arch Biochem Biophys 494:7–14PubMedGoogle Scholar
  128. 128.
    Zhang X, Gao F, Yu LL, Peng Y, Liu HH, Liu JY, Yin M, Ni J (2008) Dual functions of a monoclonal antibody against cell surface F1F0 ATP synthase on both HUVEC and tumor cells. Acta Pharmacol Sin 29:942–950PubMedGoogle Scholar
  129. 129.
    Stagg J, Divisekera U, McLaughlin N, Sharkey J, Pommey S, Denoyer D, Dwyer KM, Smyth MJ (2010) Anti-CD73 antibody therapy inhibits breast tumor growth and metastasis. Proc Natl Acad Sci U S A 107:1547–1552PubMedPubMedCentralGoogle Scholar
  130. 130.
    Wang L, Zhou X, Zhou T, Ma D, Chen S, Zhi X, Yin L, Shao Z, Ou Z, Zhou P (2008) Ecto-5′-nucleotidase promotes invasion, migration and adhesion of human breast cancer cells. J Cancer Res Clin Oncol 134:365–372PubMedGoogle Scholar
  131. 131.
    Coleman RE (2004) The role of bisphosphonates in breast cancer. Breast 13(Suppl 1):S19–S28PubMedGoogle Scholar
  132. 132.
    Varani K, Vincenzi F, Targa M, Paradiso B, Parrilli A, Fini M, Lanza G, Borea PA (2013) The stimulation of A3 adenosine receptors reduces bone-residing breast cancer in a rat preclinical model. Eur J Cancer 49:482–491PubMedGoogle Scholar
  133. 133.
    Fehm T, Zwirner M, Wallwiener D, Seeger H, Neubauer H (2012) Antitumor activity of zoledronic acid in primary breast cancer cells determined by the ATP tumor chemosensitivity assay. BMC Cancer 12:308PubMedPubMedCentralGoogle Scholar
  134. 134.
    Schott S, Wallwiener M, Kootz B, Seeger H, Fehm T, Neubauer H (2012) Cytotoxicity of the new antimetabolite-bisphosphonate (5-FdU-alendronate) in comparison to standard therapeutics on breast and ovarian cancer cell lines in the ATP tumor chemosensitivity assay. Invest New Drugs 30:1750–1755PubMedGoogle Scholar
  135. 135.
    Huang TC, Chang HY, Hsu CH, Kuo WH, Chang KJ, Juan HF (2008) Targeting therapy for breast carcinoma by ATP synthase inhibitor aurovertin B. J Proteome Res 7:1433–1444PubMedGoogle Scholar
  136. 136.
    Kawai Y, Kaidoh M, Ohhashi T (2008) MDA-MB-231 produces ATP-mediated ICAM-1-dependent facilitation of the attachment of carcinoma cells to human lymphatic endothelial cells. Am J Physiol Cell Physiol 295:C1123–C1132PubMedGoogle Scholar
  137. 137.
    Buxton IL, Yokdang N, Matz RM (2010) Purinergic mechanisms in breast cancer support intravasation, extravasation and angiogenesis. Cancer Lett 291:131–141PubMedPubMedCentralGoogle Scholar
  138. 138.
    Patel V, Rumney R, Wang N, Hipskind RH, Gallagher JA, Gartland A (2008) The effect of ATP, alone and in combination with EGF, on breast cancer cell survival. Purinergic Signalling 4:S205Google Scholar
  139. 139.
    Lee KL, Dai Q, Hansen EL, Saner CN, Price TM (2010) Modulation of ATP-induced calcium signaling by progesterone in T47D-Y breast cancer cells. Mol Cell Endocrinol 319:109–115PubMedPubMedCentralGoogle Scholar
  140. 140.
    Pubill D, Dayanithi G, Siatka C, András M, Dufour MN, Guillon G, Mendre C (2001) ATP induces intracellular calcium increases and actin cytoskeleton disaggregation via P2x receptors. Cell Calcium 29:299–309PubMedGoogle Scholar
  141. 141.
    Vandewalle B, Hornez L, Revillion F, Lefebvre J (1994) Effect of extracellular ATP on breast tumor cell growth, implication of intracellular calcium. Cancer Lett 85:47–54PubMedGoogle Scholar
  142. 142.
    Tafani M, Schito L, Pellegrini L, Villanova L, Marfe G, Anwar T, Rosa R, Indelicato M, Fini M, Pucci B, Russo MA (2011) Hypoxia-increased RAGE and P2X7R expression regulates tumor cell invasion through phosphorylation of Erk1/2 and Akt and nuclear translocation of NF-κB. Carcinogenesis 32:1167–1175PubMedGoogle Scholar
  143. 143.
    Davis FM, Kenny PA, Soo ET, van Denderen BJ, Thompson EW, Cabot PJ, Parat MO, Roberts-Thomson SJ, Monteith GR (2011) Remodeling of purinergic receptor-mediated Ca2+ signaling as a consequence of EGF-induced epithelial-mesenchymal transition in breast cancer cells. PLoS One 6:e23464PubMedPubMedCentralGoogle Scholar
  144. 144.
    Abraham EH, Vos P, Kahn J, Grubman SA, Jefferson DM, Ding I, Okunieff P (1996) Cystic fibrosis hetero- and homozygosity is associated with inhibition of breast cancer growth. Nat Med 2:593–596PubMedGoogle Scholar
  145. 145.
    Clark JH, Broadley KJ, Hutcheson IR, Nicholson RI, Kidd EJ (2003) Expression of adenosine receptors in MCF-7 human breast cancer cells. Brit J Pharmacol 138:130PGoogle Scholar
  146. 146.
    Panjehpour M, Hemati S, Forghani MA (2012) Expression of A1 and A3 adenosine receptors in human breast tumors. Tumori 98:137–141PubMedGoogle Scholar
  147. 147.
    Mujoomdar M, Bennett A, Hoskin D, Blay J (2004) Adenosine stimulation of proliferation of breast carcinoma cell lines: evaluation of the [3H]thymidine assay system and modulatory effects of the cellular microenvironment in vitro. J Cell Physiol 201:429–438PubMedGoogle Scholar
  148. 148.
    Lu J, Pierron A, Ravid K (2003) An adenosine analogue, IB-MECA, down-regulates estrogen receptor alpha and suppresses human breast cancer cell proliferation. Cancer Res 63:6413–6423PubMedGoogle Scholar
  149. 149.
    Panjehpour M, Karami-Tehrani F (2004) An adenosine analog (IB-MECA) inhibits anchorage-dependent cell growth of various human breast cancer cell lines. Int J Biochem Cell Biol 36:1502–1509PubMedGoogle Scholar
  150. 150.
    Hashemi M, Karami-Tehrani F, Ghavami S, Maddika S, Los M (2005) Adenosine and deoxyadenosine induces apoptosis in oestrogen receptor-positive and -negative human breast cancer cells via the intrinsic pathway. Cell Prolif 38:269–285PubMedGoogle Scholar
  151. 151.
    Mirza A, Basso A, Black S, Malkowski M, Kwee L, Pachter JA, Lachowicz JE, Wang Y, Liu S (2005) RNA interference targeting of A1 receptor-overexpressing breast carcinoma cells leads to diminished rates of cell proliferation and induction of apoptosis. Cancer Biol Ther 4:1355–1360PubMedGoogle Scholar
  152. 152.
    Panjehpour M, Castro M, Klotz KN (2005) Human breast cancer cell line MDA-MB-231 expresses endogenous A2B adenosine receptors mediating a Ca2+ signal. Br J Pharmacol 145:211–218PubMedPubMedCentralGoogle Scholar
  153. 153.
    Cekic C, Sag D, Li Y, Theodorescu D, Strieter RM, Linden J (2012) Adenosine A2B receptor blockade slows growth of bladder and breast tumors. J Immunol 188:198–205PubMedGoogle Scholar
  154. 154.
    Sadej R, Inai K, Rajfur Z, Ostapkowicz A, Kohler J, Skladanowski AC, Mitchell BS, Spychala J (2008) Tenascin C interacts with ecto-5′-nucleotidase (eN) and regulates adenosine generation in cancer cells. Biochim Biophys Acta 1782:35–40PubMedGoogle Scholar
  155. 155.
    Aghaei M, Karami-Tehrani F, Salami S, Atri M (2010) Diagnostic value of adenosine deaminase activity in benign and malignant breast tumors. Arch of Med Res 41:14–18Google Scholar
  156. 156.
    Harris JW, Wong YP, Kehe CR, Teng SS (1975) The role of adenosine triphosphate, chalones, and specific proteins in controlling tumor growth fraction. Cancer Res 35:3181–3186PubMedGoogle Scholar
  157. 157.
    Artalejo AR, Garcia-Sancho J (1988) Mobilization of intracellular calcium by extracellular ATP and by calcium ionophores in the Ehrlich ascites-tumour cell. Biochim Biophys Acta 941:48–54PubMedGoogle Scholar
  158. 158.
    Ueno H, Tezuka M, Tamemasa O (1984) Effect of adenosine triphosphate on the proliferation of cultured tumor cells. Yakugaku Zasshi 104:1207–1210PubMedGoogle Scholar
  159. 159.
    Lasso De la Vega M, Terradez P, Obrador E, Navarro J, Pellicer JA, Estrela JM (1994) Inhibition of cancer growth and selective glutathione depletion in Ehrlich tumour cells in vivo by extracellular ATP. Biochem J 298:99–105PubMedPubMedCentralGoogle Scholar
  160. 160.
    Dubyak GR (1986) Extracellular ATP activates polyphosphoinositide breakdown and Ca2+ mobilization in Ehrlich ascites tumor cells. Arch Biochem Biophys 245:84–95PubMedGoogle Scholar
  161. 161.
    Estrela JM, Obrador E, Navarro J, Lasso De la Vega M, Pellicer JA (1995) Elimination of Ehrlich tumours by ATP-induced growth inhibition, glutathione depletion and X-rays. Nat Med 1:84–88PubMedGoogle Scholar
  162. 162.
    Pedersen SF, Pedersen S, Lambert IH, Hoffmann EK (1998) P2 receptor-mediated signal transduction in Ehrlich ascites tumor cells. Biochim Biophys Acta 1374:94–106PubMedGoogle Scholar
  163. 163.
    Pedersen S, Pedersen SF, Nilius B, Lambert IH, Hoffmann EK (1999) Mechanical stress induces release of ATP from Ehrlich ascites tumor cells. Biochim Biophys Acta 1416:271–284PubMedGoogle Scholar
  164. 164.
    Zinchenko VP, Kasymov VA, Li VV, Kaimachnikov NP (2005) The calmodulin inhibitor R24571 induces a short-term Ca2+ entry and a pulse-like secretion of ATP in Ehrlich ascites tumor cells. Biofizika 50:1055–1069PubMedGoogle Scholar
  165. 165.
    Zamay TN, Zamay AS (2006) Influence of ATP on Ehrlich ascites carcinoma cell free cytoplasmic calcium concentration in the course of tumor growth. Biochemistry (Mosc) 71:1090–1095Google Scholar
  166. 166.
    Fang WG, Pirnia F, Bang YJ, Myers CE, Trepel JB (1992) P2-purinergic receptor agonists inhibit the growth of androgen-independent prostate carcinoma cells. J Clin Invest 89:191–196PubMedPubMedCentralGoogle Scholar
  167. 167.
    Wasilenko WJ, Cooper J, Palad AJ, Somers KD, Blackmore PF, Rhim JS, Wright GL Jr, Schellhammer PF (1997) Calcium signaling in prostate cancer cells: evidence for multiple receptors and enhanced sensitivity to bombesin/GRP. Prostate 30:167–173PubMedGoogle Scholar
  168. 168.
    Vanoverberghe K, Mariot P, Vanden Abeele F, Delcourt P, Parys JB, Prevarskaya N (2003) Mechanisms of ATP-induced calcium signaling and growth arrest in human prostate cancer cells. Cell Calcium 34:75–85PubMedGoogle Scholar
  169. 169.
    Dainty IA, Franklin M, McKechnie KCW (1995) Classification of P2-purinoceptors on a human prostate cancer cell line (PC3 cells). Brit J Pharmacol 114:106PGoogle Scholar
  170. 170.
    Janssens R, Communi D, Pirotton S, Samson M, Parmentier M, Boeynaems JM (1996) Cloning and tissue distribution of the human P2Y1 receptor. Biochem Biophys Res Commun 221:588–593PubMedGoogle Scholar
  171. 171.
    Wei Q, Costanzi S, Liu QZ, Gao ZG, Jacobson KA (2011) Activation of the P2Y1 receptor induces apoptosis and inhibits proliferation of prostate cancer cells. Biochem Pharmacol 82:418–425PubMedPubMedCentralGoogle Scholar
  172. 172.
    Tapia-Vieyra JV, Mas-Oliva J (2001) Apoptosis and cell death channels in prostate cancer. Arch Med Res 32:175–185PubMedGoogle Scholar
  173. 173.
    Janssens R, Boeynaems JM (2001) Effects of extracellular nucleotides and nucleosides on prostate carcinoma cells. Br J Pharmacol 132:536–546PubMedPubMedCentralGoogle Scholar
  174. 174.
    Sauer H, Stanelle R, Hescheler J, Wartenberg M (2002) The DC electrical-field-induced Ca2+ response and growth stimulation of multicellular tumor spheroids are mediated by ATP release and purinergic receptor stimulation. J Cell Sci 115:3265–3273PubMedGoogle Scholar
  175. 175.
    Ye ZW, Ghalali A, Högberg J, Stenius U (2011) Silencing p110β prevents rapid depletion of nuclear pAkt. Biochem Biophys Res Commun 415:613–618PubMedGoogle Scholar
  176. 176.
    Limami Y, Pinon A, Leger DY, Pinault E, Delage C, Beneytout JL, Simon A, Liagre B (2012) The P2Y2/Src/p38/COX-2 pathway is involved in the resistance to ursolic acid-induced apoptosis in colorectal and prostate cancer cells. Biochimie 94:1754–1763PubMedGoogle Scholar
  177. 177.
    Chen L, He HY, Li HM, Zheng J, Heng WJ, You JF, Fang WG (2004) ERK1/2 and p38 pathways are required for P2Y receptor-mediated prostate cancer invasion. Cancer Lett 215:239–247PubMedGoogle Scholar
  178. 178.
    Nandigama R, Padmasekar M, Wartenberg M, Sauer H (2006) Feed forward cycle of hypotonic stress-induced ATP release, purinergic receptor activation, and growth stimulation of prostate cancer cells. J Biol Chem 281:5686–5693PubMedGoogle Scholar
  179. 179.
    Sauer H, Hescheler J, Wartenberg M (2000) Mechanical strain-induced Ca2+ waves are propagated via ATP release and purinergic receptor activation. Am J Physiol Cell Physiol 279:C295–C307PubMedGoogle Scholar
  180. 180.
    Zhang Y, Gong LH, Zhang HQ, Du Q, You JF, Tian XX, Fang WG (2010) Extracellular ATP enhances in vitro invasion of prostate cancer cells by activating Rho GTPase and upregulating MMPs expression. Cancer Lett 293:189–197PubMedGoogle Scholar
  181. 181.
    Stagg J, Beavis PA, Divisekera U, Liu MC, Moller A, Darcy PK, Smyth MJ (2012) CD73-deficient mice are resistant to carcinogenesis. Cancer Res 72:2190–2196PubMedGoogle Scholar
  182. 182.
    Shabbir M, Ryten M, Thompson CS, Mikhailidis DP, Burnstock G (2008) Characterisation of calcium-independent purinergic receptor-mediated apoptosis in hormone refractory prostate cancer. BJU Int 101:352–359PubMedGoogle Scholar
  183. 183.
    Fernando KC, Gargett CE, Wiley JS (1999) Activation of the P2Z/P2X7 receptor in human lymphocytes produces a delayed permeability lesion: involvement of phospholipase D. Arch Biochem Biophys 362:197–202PubMedGoogle Scholar
  184. 184.
    Shemon AN, Sluyter R, Fernando SL, Clarke AL, Dao-Ung LP, SkarRatt KK, Saunders BM, Tan KS, Gu BJ, Fuller SJ, Britton WJ, Petrou S, Wiley JS (2006) A Thr357 to Ser polymorphism in homozygous and compound heterozygous subjects causes absent or reduced P2X7 function and impairs ATP-induced mycobacterial killing by macrophages. J Biol Chem 281:2079–2086PubMedGoogle Scholar
  185. 185.
    Fuller SJ, Stokes L, SkarRatt KK, Gu BJ, Wiley JS (2009) Genetics of the P2X7 receptor and human disease. Purinergic Signal 5:257–262PubMedPubMedCentralGoogle Scholar
  186. 186.
    Slater M, Danieletto S, Gidley-Baird A, Teh LC, Barden JA (2004) Early prostate cancer detected using expression of non-functional cytolytic P2X7 receptors. Histopathology 44:206–215PubMedGoogle Scholar
  187. 187.
    Slater M, Danieletto S, Barden JA (2005) Expression of the apoptotic calcium channel P2X7 in the glandular epithelium. J Mol Histol 36:159–165PubMedGoogle Scholar
  188. 188.
    Kyprianou N, Isaacs JT (1989) "Thymineless" death in androgen-independent prostatic cancer cells. Biochem Biophys Res Commun 165:73–81PubMedGoogle Scholar
  189. 189.
    Martikainen P, Kyprianou N, Tucker RW, Isaacs JT (1991) Programmed death of nonproliferating androgen-independent prostatic cancer cells. Cancer Res 51:4693–4700PubMedGoogle Scholar
  190. 190.
    Abraham EH, Salikhova A, Sterling KM, Johnston N (2001) Modulation of ATP release rates from erythrocytes in blood samples from prostate cancer patients receiving radiation therapy: implications to iv ATP therapy. Radiology 266Google Scholar
  191. 191.
    Miyake H, Hara I, Yamanaka K, Arakawa S, Kamidono S (1999) Calcium ionophore, ionomycin inhibits growth of human bladder cancer cells both in vitro and in vivo with alteration of Bcl-2 and Bax expression levels. J Urol 162:916–921PubMedGoogle Scholar
  192. 192.
    Lissbrant IF, Lissbrant E, Damber JE, Bergh A (2001) Blood vessels are regulators of growth, diagnostic markers and therapeutic targets in prostate cancer. Scand J Urol Nephrol 35:437–452PubMedGoogle Scholar
  193. 193.
    Aweimer A, Stachon T, Tannapfel A, Köller M, Truss MC, Stachon A (2012) Regulation of soluble VEGFR-2 secreted by microvascular endothelial cells derived from human BPH. Prostate Cancer Prostatic Dis 15:157–164PubMedGoogle Scholar
  194. 194.
    Minelli A, Bellezza I, Agostini M, Bracarda S, Culig Z (2006) Mechanism of 2-chloroadenosine toxicity to PC3 cell line. Prostate 66:1425–1436PubMedGoogle Scholar
  195. 195.
    Minelli A, Bellezza I, Tucci A, Rambotti MG, Conte C, Culig Z (2009) Differential involvement of reactive oxygen species and nucleoside transporters in cytotoxicity induced by two adenosine analogues in human prostate cancer cells. Prostate 69:538–547PubMedGoogle Scholar
  196. 196.
    Aghaei M, Panjehpour M, Karami-Tehrani F, Salami S (2011) Molecular mechanisms of A3 adenosine receptor-induced G1 cell cycle arrest and apoptosis in androgen-dependent and independent prostate cancer cell lines: involvement of intrinsic pathway. J Cancer Res Clin Oncol 137:1511–1523PubMedGoogle Scholar
  197. 197.
    Aghaei M, Karami-Tehrani F, Panjehpour M, Salami S, Fallahian F (2012) Adenosine induces cell-cycle arrest and apoptosis in androgen-dependent and -independent prostate cancer cell lines, LNcap-FGC-10, DU-145, and PC3. Prostate 72:361–375PubMedGoogle Scholar
  198. 198.
    Jajoo S, Mukherjea D, Watabe K, Ramkumar V (2009) Adenosine A3 receptor suppresses prostate cancer metastasis by inhibiting NADPH oxidase activity. Neoplasia 11:1132–1145PubMedPubMedCentralGoogle Scholar
  199. 199.
    Rapaport E, Fishman RF, Gercel C (1983) Growth inhibition of human tumor cells in soft-agar cultures by treatment with low levels of adenosine 5′-triphosphate. Cancer Res 43:4402–4406PubMedGoogle Scholar
  200. 200.
    Hitchin BW, Dobson PR, Ruprai A, Hardcastle J, Hardcastle PT, Taylor CJ, Brown BL (1991) Purinoceptors and second messenger signalling in the human colonic adenoma cell line. J Physiol 438:80PGoogle Scholar
  201. 201.
    Lohrmann E, Cabantchik ZI, Greger R (1992) Transmitter-induced changes of the membrane voltage of HT29 cells. Pflügers Arch 421:224–229PubMedGoogle Scholar
  202. 202.
    Correale P, Caraglia M, Procopio A, Marinetti MR, Guarrasi R, Fabbrocini A, Bianco AR, Tagliaferri P (1993) Transmembrane ion flux modifiers verapamil and ouabain modulate cytotoxic effects of extracellular ATP on human tumor cells in vitro. Int J Oncol 3:847–851PubMedGoogle Scholar
  203. 203.
    Parr CE, Sullivan DM, Paradiso AM, Lazarowski ER, Burch LH, Olsen JC, Erb L, Weisman GA, Boucher RC, Turner JT (1994) Cloning and expression of a human P2U nucleotide receptor, a target for cystic fibrosis pharmacotherapy. Proc Natl Acad Sci U S A 91:13067PubMedGoogle Scholar
  204. 204.
    Richards M, van Giersbergen P, Zimmermann A, Lesur B, Hoflack J (1997) Activation of neurotensin receptors and purinoceptors in human colonic adenocarcinoma cells detected with the microphysiometer. Biochem Pharmacol 54:825–832PubMedGoogle Scholar
  205. 205.
    Guo X, Merlin D, Harvey RD, Laboisse C, Hopfer U (1995) Stimulation of Cl secretion by extracellular ATP does not depend on increased cytosolic Ca2+ in HT-29.cl16E. Am J Physiol 269:C1457–C1463PubMedGoogle Scholar
  206. 206.
    Guo XW, Merlin D, Laboisse C, Hopfer U (1997) Purinergic agonists, but not cAMP, stimulate coupled granule fusion and Cl conductance in HT29-Cl.16E. Am J Physiol 273:C804–C809PubMedGoogle Scholar
  207. 207.
    Dho S, Stewart K, Foskett JK (1992) Purinergic receptor activation of Cl secretion in T84 cells. Am J Physiol 262:C67–C74PubMedGoogle Scholar
  208. 208.
    Zhang W, Roomans GM (1997) Regulation of ion transport by P2U purinoceptors and α2A adrenoceptors in HT29 cells. Cell Biol Int 4:195–200Google Scholar
  209. 209.
    Höpfner M, Lemmer K, Jansen A, Hanski C, Riecken EO, Gavish M, Mann B, Buhr H, Glassmeier G, Scherübl H (1998) Expression of functional P2-purinergic receptors in primary cultures of human colorectal carcinoma cells. Biochem Biophys Res Commun 251:811–817PubMedGoogle Scholar
  210. 210.
    Höpfner M, Maaser K, Barthel B, von Lampe B, Hanski C, Riecken EO, Zeitz M, Scherubl H (2001) Growth inhibition and apoptosis induced by P2Y2 receptors in human colorectal carcinoma cells: involvement of intracellular calcium and cyclic adenosine monophosphate. Int J Colorectal Dis 16:154–166PubMedGoogle Scholar
  211. 211.
    Yaguchi T, Saito M, Yasuda Y, Kanno T, Nakano T, Nishizaki T (2010) Higher concentrations of extracellular ATP suppress proliferation of Caco-2 human colonic cancer cells via an unknown receptor involving PKC inhibition. Cell Physiol Biochem 26:125–134PubMedGoogle Scholar
  212. 212.
    Cummins MM, O’Mullane LM, Barden JA, Cook DI, Poronnik P (2000) Purinergic responses in HT29 colonic epithelial cells are mediated by G protein α-subunits. Cell Calcium 27:247–255PubMedGoogle Scholar
  213. 213.
    McAlroy HL, Ahmed S, Day SM, Baines DL, Wong HY, Yip CY, Ko WH, Wilson SM, Collett A (2000) Multiple P2Y receptor subtypes in the apical membranes of polarized epithelial cells. Br J Pharmacol 131:1651–1658PubMedPubMedCentralGoogle Scholar
  214. 214.
    Buzzi N, Bilbao PS, Boland R, de Boland AR (2009) Extracellular ATP activates MAP kinase cascades through a P2Y purinergic receptor in the human intestinal Caco-2 cell line. Biochim Biophys Acta 1790:1651–1659PubMedGoogle Scholar
  215. 215.
    Ullrich N, Caplanusi A, Brône B, Hermans D, Larivière E, Nilius B, Van Driessche W, Eggermont J (2006) Stimulation by caveolin-1 of the hypotonicity-induced release of taurine and ATP at basolateral, but not apical, membrane of Caco-2 cells. Am J Physiol Cell Physiol 290:C1287–C1296PubMedGoogle Scholar
  216. 216.
    Nylund G, Nordgren S, Delbro DS (2004) Expression of P2Y2 purinoceptors in MCG 101 murine sarcoma cells, and HT-29 human colon carcinoma cells. Auton Neurosci 112:69–79PubMedGoogle Scholar
  217. 217.
    Nylund G, Hultman L, Nordgren S, Delbro DS (2007) P2Y2- and P2Y4 purinergic receptors are over-expressed in human colon cancer. Auton Autacoid Pharmacol 27:79–84PubMedGoogle Scholar
  218. 218.
    Hu H, O’Mullane LM, Cummins MM, Campbell CR, Hosoda Y, Poronnik P, Dinudom A, Cook DI (2010) Negative regulation of Ca2+ influx during P2Y2 purinergic receptor activation is mediated by Gβγ-subunits. Cell Calcium 47:55–64PubMedGoogle Scholar
  219. 219.
    Hatanaka H, Takada S, Choi YL, Fujiwara S, Soda M, Enomoto M, Kurashina K, Watanabe H, Yamashita Y, Sugano K, Mano H (2007) Transforming activity of purinergic receptor P2Y, G-protein coupled, 2 revealed by retroviral expression screening. Biochem Biophys Res Commun 356:723–726PubMedGoogle Scholar
  220. 220.
    Buzzi N, Boland R, Russo de Boland A (2010) Signal transduction pathways associated with ATP-induced proliferation of colon adenocarcinoma cells. Biochim Biophys Acta 1800:946–955PubMedGoogle Scholar
  221. 221.
    Hinoshita E, Uchiumi T, Taguchi K, Kinukawa N, Tsuneyoshi M, Maehara Y, Sugimachi K, Kuwano M (2000) Increased expression of an ATP-binding cassette superfamily transporter, multidrug resistance protein 2, in human colorectal carcinomas. Clin Cancer Res 6:2401–2407PubMedGoogle Scholar
  222. 222.
    Künzli BM, Bernlochner MI, Rath S, Käser S, Csizmadia E, Enjyoji K, Cowan P, d’Apice A, Dwyer K, Rosenberg R, Perren A, Friess H, Maurer CA, Robson SC (2011) Impact of CD39 and purinergic signalling on the growth and metastasis of colorectal cancer. Purinergic Signal 7:231–241PubMedPubMedCentralGoogle Scholar
  223. 223.
    Eroglu A, Canbolat O, Demirci S, Kocaoglu H, Eryavuz Y, Akgül H (2000) Activities of adenosine deaminase and 5′-nucleotidase in cancerous and noncancerous human colorectal tissues. Med Oncol 17:319–324PubMedGoogle Scholar
  224. 224.
    ten Kate J, Wijnen JT, van der Goes RG, Quadt R, Griffioen G, Bosman FT, Khan PM (1984) Quantitative changes in adenosine deaminase isoenzymes in human colorectal adenocarcinomas. Cancer Res 44:4688–4692PubMedGoogle Scholar
  225. 225.
    Tan EY, Mujoomdar M, Blay J (2004) Adenosine down-regulates the surface expression of dipeptidyl peptidase IV on HT-29 human colorectal carcinoma cells: implications for cancer cell behavior. Am J Pathol 165:319–330PubMedPubMedCentralGoogle Scholar
  226. 226.
    Giglioni S, Leoncini R, Aceto E, Chessa A, Civitelli S, Bernini A, Tanzini G, Carraro F, Pucci A, Vannoni D (2008) Adenosine kinase gene expression in human colorectal cancer. Nucleosides Nucleotides Nucleic Acids 27:750–754PubMedGoogle Scholar
  227. 227.
    Whitehouse PA, Knight LA, Di NF, Mercer SJ, Sharma S, Cree IA (2003) Heterogeneity of chemosensitivity of colorectal adenocarcinoma determined by a modified ex vivo ATP-tumor chemosensitivity assay (ATP-TCA). Anticancer Drugs 14:369–375PubMedGoogle Scholar
  228. 228.
    Cho YB, Lee WY, Song SY, Choi SH, Shin HJ, Ahn KD, Lee JM, Kim HC, Yun SH, Chun HK (2009) In vitro chemosensitivity based on depth of invasion in advanced colorectal cancer using ATP-based chemotherapy response assay (ATP-CRA). Eur J Surg Oncol 35:951–956PubMedGoogle Scholar
  229. 229.
    Huh JW, Park YA, Lee KY, Sohn SK (2009) Heterogeneity of adenosine triphosphate-based chemotherapy response assay in colorectal cancer—secondary publication. Yonsei Med J 50:697–703PubMedPubMedCentralGoogle Scholar
  230. 230.
    Selzner N, Selzner M, Graf R, Ungethuem U, Fitz JG, Clavien PA (2004) Water induces autocrine stimulation of tumor cell killing through ATP release and P2 receptor binding. Cell Death Differ 11(Suppl 2):S172–S180PubMedGoogle Scholar
  231. 231.
    Linden J (2006) Adenosine metabolism and cancer. Focus on "Adenosine downregulates DPPIV on HT-29 colon cancer cells by stimulating protein tyrosine phosphatases and reducing ERK1/2 activity via a novel pathway". Am J Physiol Cell Physiol 291:C405–C406PubMedGoogle Scholar
  232. 232.
    Lelièvre V, Muller JM, Falcòn J (1998) Adenosine modulates cell proliferation in human colonic adenocarcinoma. I. Possible involvement of adenosine A1 receptor subtypes in HT29 cells. Eur J Pharmacol 341:289–297PubMedGoogle Scholar
  233. 233.
    Lelièvre V, Muller JM, Falcòn J (1998) Adenosine modulates cell proliferation in human colonic carcinoma. II. Differential behavior of HT29, DLD-1, Caco-2 and SW403 cell lines. Eur J Pharmacol 341:299–308PubMedGoogle Scholar
  234. 234.
    Mujoomdar M, Hoskin D, Blay J (2003) Adenosine stimulation of the proliferation of colorectal carcinoma cell lines. Roles of cell density and adenosine metabolism. Biochem Pharmacol 66:1737–1747PubMedGoogle Scholar
  235. 235.
    Saito M, Yaguchi T, Yasuda Y, Nakano T, Nishizaki T (2010) Adenosine suppresses CW2 human colonic cancer growth by inducing apoptosis via A1 adenosine receptors. Cancer Lett 290:211–215PubMedGoogle Scholar
  236. 236.
    Ma DF, Kondo T, Nakazawa T, Niu DF, Mochizuki K, Kawasaki T, Yamane T, Katoh R (2010) Hypoxia-inducible adenosine A2B receptor modulates proliferation of colon carcinoma cells. Hum Pathol 41:1550–1557PubMedGoogle Scholar
  237. 237.
    Cheng Y, Yang J, Agarwal R, Green GM, Mease RC, Pomper MG, Meltzer SJ, Abraham JM (2011) Strong inhibition of xenografted tumor growth by low-level doses of [32P]ATP. Oncotarget 2:461–466PubMedPubMedCentralGoogle Scholar
  238. 238.
    Carlson CC, Chinery R, Burnham LL, Dransfield DT (2000) 8-Cl-adenosine-induced inhibition of colorectal cancer growth in vitro and in vivo. Neoplasia 2:441–448PubMedPubMedCentralGoogle Scholar
  239. 239.
    Ohana G, Bar-Yehuda S, Arich A, Madi L, Dreznick Z, Rath-Wolfson L, Silberman D, Slosman G, Fishman P (2003) Inhibition of primary colon carcinoma growth and liver metastasis by the A3 adenosine receptor agonist CF101. Br J Cancer 89:1552–1558PubMedPubMedCentralGoogle Scholar
  240. 240.
    Fishman P, Bar-Yehuda S, Ohana G, Barer F, Ochaion A, Erlanger A, Madi L (2004) An agonist to the A3 adenosine receptor inhibits colon carcinoma growth in mice via modulation of GSK-3β and NF-κB. Oncogene 23:2465–2471PubMedGoogle Scholar
  241. 241.
    Gessi S, Merighi S, Varani K, Cattabriga E, Benini A, Mirandola P, Leung E, Mac Lennan S, Feo C, Baraldi S, Borea PA (2007) Adenosine receptors in colon carcinoma tissues and colon tumoral cell lines: focus on the A3 adenosine subtype. J Cell Physiol 211:826–836PubMedGoogle Scholar
  242. 242.
    Stemmer SM, Shani A, Klein B, Silverman MH, Lorber I, Farbstein M, Shmueli E, Figer A (2004) A phase II, multi-center study of a new non-cytotoxic A3 adenosine receptor agonist CF101, dose-finding (randomized blinded) in patients (pts) with refractory metastatic colorectal cancer. J Clin Oncol 22:232SGoogle Scholar
  243. 243.
    Gessi S, Cattabriga E, Avitabile A, Gafa’ R, Lanza G, Cavazzini L, Bianchi N, Gambari R, Feo C, Liboni A, Gullini S, Leung E, Mac-Lennan S, Borea PA (2004) Elevated expression of A3 adenosine receptors in human colorectal cancer is reflected in peripheral blood cells. Clin Cancer Res 10:5895–5901PubMedGoogle Scholar
  244. 244.
    Giannecchini M, D’Innocenzo B, Pesi R, Sgarrella F, Iorio M, Collecchi P, Tozzi MG, Camici M (2003) 2′-Deoxyadenosine causes apoptotic cell death in a human colon carcinoma cell line. J Biochem Mol Toxicol 17:329–337PubMedGoogle Scholar
  245. 245.
    Yasuda Y, Saito M, Yamamura T, Yaguchi T, Nishizaki T (2009) Extracellular adenosine induces apoptosis in Caco-2 human colonic cancer cells by activating caspase-9/-3 via A2a adenosine receptors. J Gastroenterol 44:56–65PubMedGoogle Scholar
  246. 246.
    Richard CL, Tan EY, Blay J (2006) Adenosine upregulates CXCR4 and enhances the proliferative and migratory responses of human carcinoma cells to CXCL12/SDF-1α. Int J Cancer 119:2044–2053PubMedGoogle Scholar
  247. 247.
    Tan EY, Richard CL, Zhang H, Hoskin DW, Blay J (2006) Adenosine downregulates DPPIV on HT-29 colon cancer cells by stimulating protein tyrosine phosphatase(s) and reducing ERK1/2 activity via a novel pathway. Am J Physiol Cell Physiol 291:C433–C444PubMedGoogle Scholar
  248. 248.
    Merighi S, Benini A, Mirandola P, Gessi S, Varani K, Simioni C, Leung E, Maclennan S, Baraldi PG, Borea PA (2007) Caffeine inhibits adenosine-induced accumulation of hypoxia-inducible factor-1α, vascular endothelial growth factor, and interleukin-8 expression in hypoxic human colon cancer cells. Mol Pharmacol 72:395–406PubMedGoogle Scholar
  249. 249.
    Hamada E, Imai Y, Hazama H, Takahashi M, Nakajima T, Ota S, Terano A, Omata M, Kurachi Y (1993) P2-purinergic receptor in human gastric signet ring cell carcinoma cell line: a patch clamp study. Gastroenterology 104:A829Google Scholar
  250. 250.
    Saitoh M, Nagai K, Nakagawa K, Yamamura T, Yamamoto S, Nishizaki T (2004) Adenosine induces apoptosis in the human gastric cancer cells via an intrinsic pathway relevant to activation of AMP-activated protein kinase. Biochem Pharmacol 67:2005–2011PubMedGoogle Scholar
  251. 251.
    Wang MX, Ren LM (2006) Growth inhibitory effect and apoptosis induced by extracellular ATP and adenosine on human gastric carcinoma cells: involvement of intracellular uptake of adenosine. Acta Pharmacol Sin 27:1085–1092PubMedGoogle Scholar
  252. 252.
    Park JY, Kim YS, Bang S, Hyung WJ, Noh SH, Choi SH, Song SY (2007) ATP-based chemotherapy response assay in patients with unresectable gastric cancer. Oncology 73:439–440PubMedGoogle Scholar
  253. 253.
    Lee JH, Kim MC, Oh SY, Kwon HC, Kim SH, Kwon KA, Lee S, Jeong JS, Choi SR, Kim HJ (2011) Predictive value of in vitro adenosine triphosphate-based chemotherapy response assay in advanced gastric cancer patients who received oral 5-fluorouracil after curative resection. Cancer Res Treat 43:117–123PubMedPubMedCentralGoogle Scholar
  254. 254.
    Saha A, Hammond CE, Gooz M, Smolka AJ (2008) The role of Sp1 in IL-1β and H. pylori-mediated regulation of H,K-ATPase gene transcription. Am J Physiol Gastrointest Liver Physiol 295:G977–G986PubMedPubMedCentralGoogle Scholar
  255. 255.
    Cornberg M, Schoefl C, Jandl O, Potthoff A, Mix H, Goeke M, Beil W, Manns MP, Wagner S (2000) Differential expression of the adenosine receptor subtypes in human gastric mucosa and cancer cells. Gastroenterology 118:A304Google Scholar
  256. 256.
    Ling ZQ, Qi CJ, Lu XX, Qian LJ, Gu LH, Zheng ZG, Zhao Q, Wang S, Fang XH, Yang ZX, Yin J, Mao WM (2012) Heterogeneity of chemosensitivity in esophageal cancer using ATP-tumor chemosensitivity assay. Acta Pharmacol Sin 33:401–406PubMedGoogle Scholar
  257. 257.
    Kalhan A, Kidd M, Modlin I, Pfragner R, Rees DA, Ham J (2009) Adenosine A2 receptor signalling mediates chromogranin A secretion from neuroendocrine tumours. Neuroendocrinology 90:119Google Scholar
  258. 258.
    Elsing C, Georgiev T, Hubner CA, Boger R, Stremmel W, Schlenker T (2012) Extracellular ATP induces cytoplasmic and nuclear Ca2+ transients via P2Y2 receptor in human biliary epithelial cancer cells (Mz-Cha-1). Anticancer Res 32:3759–3767PubMedGoogle Scholar
  259. 259.
    Clunes MT, Kemp PJ (1996) P2U purinoceptor modulation of intracellular Ca2+ in a human lung adenocarcinoma cell line: down-regulation of Ca2+ influx by protein kinase C. Cell Calcium 20:339–346PubMedGoogle Scholar
  260. 260.
    Remsbury A, Rakhit S, Wilson SM (1996) P2U receptor agonists do not inhibit forskolin-evoked cAMP accumulation in A549 lung adenocarcinoma cells. J Physiol 495:179PGoogle Scholar
  261. 261.
    Tatur S, Kreda S, Lazarowski E, Grygorczyk R (2008) Calcium-dependent release of adenosine and uridine nucleotides from A549 cells. Purinergic Signal 4:139–146PubMedPubMedCentralGoogle Scholar
  262. 262.
    Zhao DM, Xue HH, Chida K, Suda T, Oki Y, Kanai M, Uchida C, Ichiyama A, Nakamura H (2000) Effect of erythromycin on ATP-induced intracellular calcium response in A549 cells. Am J Physiol Lung Cell Mol Physiol 278:L726–L736PubMedGoogle Scholar
  263. 263.
    Miki K, Tanaka H, Nagai Y, Kimura C, Oike M (2010) Transforming growth factor β1 alters calcium mobilizing properties and endogenous ATP release in A549 cells: possible implications for cell migration. J Pharmacol Sci 113:387–394PubMedGoogle Scholar
  264. 264.
    Agteresch HJ, Dagnelie PC, van der Gaast A, Stijnen T, Wilson JH (2000) Randomized clinical trial of adenosine 5′-triphosphate in patients with advanced non-small-cell lung cancer. J Natl Cancer Inst 92:321–328PubMedGoogle Scholar
  265. 265.
    Dagnelie PC, Agteresch HJ (2004) Promising effects of adenosine triphosphate infusion on nutritional status and quality of life in advanced non-small-cell lung cancer: a randomized clinical trial. Drug Dev Res 59:146–151Google Scholar
  266. 266.
    Leij-Halfwerk S, Agteresch HJ, Sijens PE, Dagnelie PC (2002) Adenosine triphosphate infusion increases liver energy status in advanced lung cancer patients: an in vivo 31P magnetic resonance spectroscopy study. Hepatology 35:421–424PubMedGoogle Scholar
  267. 267.
    Hatta Y, Takahashi M, Enomoto Y, Takahashi N, Sawada U, Horie T (2004) Adenosine triphosphate (ATP) enhances the antitumor effect of etoposide (VP16) in lung cancer cells. Oncol Rep 12:1139–1142PubMedGoogle Scholar
  268. 268.
    Lin CC, Lee IT, Wu WL, Lin WN, Yang CM (2012) Adenosine triphosphate regulates NADPH oxidase activity leading to hydrogen peroxide production and COX-2/PGE2 expression in A549 cells. Am J Physiol Lung Cell Mol Physiol 303:L401–L412PubMedGoogle Scholar
  269. 269.
    Schäfer R, Hartig R, Sedehizade F, Welte T, Reiser G (2006) Adenine nucleotides inhibit proliferation of the human lung adenocarcinoma cell line LXF-289 by activation of nuclear factor κB1 and mitogen-activated protein kinase pathways. FEBS J 273:3756–3767PubMedGoogle Scholar
  270. 270.
    Moon YW, Choi SH, Kim YT, Sohn JH, Chang J, Kim SK, Park MS, Chung KY, Lee HJ, Kim JH (2007) Adenosine triphosphate-based chemotherapy response assay (ATP-CRA)-guided platinum-based 2-drug chemotherapy for unresectable nonsmall-cell lung cancer. Cancer 109:1829–1835PubMedGoogle Scholar
  271. 271.
    Moon YW, Sohn JH, Kim YT, Chang H, Jeong JH, Lee YJ, Chang J, Kim SK, Jung M, Hong S, Choi SH, Kim JH (2009) Adenosine triphosphate-based chemotherapy response assay (ATP-CRA)-guided versus empirical chemotherapy in unresectable non-small cell lung cancer. Anticancer Res 29:4243–4249PubMedGoogle Scholar
  272. 272.
    Swennen ELR, Ummels V, Bast A, Dagnelie P (2008) Increased cytotoxicity of cisplatin in a human large cell lung carcinoma cell line by ATP. Purinergic Signalling 4:S207Google Scholar
  273. 273.
    Swennen EL, Ummels V, Buss I, Jaehde U, Bast A, Dagnelie PC (2010) ATP sensitizes H460 lung carcinoma cells to cisplatin-induced apoptosis. Chem Biol Interact 184:338–345PubMedGoogle Scholar
  274. 274.
    Chang HY, Huang HC, Huang TC, Yang PC, Wang YC, Juan HF (2012) Ectopic ATP synthase blockade suppresses lung adenocarcinoma growth by activating the unfolded protein response. Cancer Res 72:4696–4706PubMedGoogle Scholar
  275. 275.
    Ryzhov S, Novitskiy SV, Zaynagetdinov R, Goldstein AE, Carbone DP, Biaggioni I, Dikov MM, Feoktistov I (2008) Host A2B adenosine receptors promote carcinoma growth. Neoplasia 10:987–995PubMedPubMedCentralGoogle Scholar
  276. 276.
    Zhang HY, Gu YY, Li ZG, Jia YH, Yuan L, Li SY, An GS, Ni JH, Jia HT (2004) Exposure of human lung cancer cells to 8-chloro-adenosine induces G2/M arrest and mitotic catastrophe. Neoplasia 6:802–812PubMedPubMedCentralGoogle Scholar
  277. 277.
    Gu YY, Zhang HY, Zhang HJ, Li SY, Ni JH, Jia HT (2006) 8-Chloro-adenosine inhibits growth at least partly by interfering with actin polymerization in cultured human lung cancer cells. Biochem Pharmacol 72:541–550PubMedGoogle Scholar
  278. 278.
    Li WJ, Gu YY, Zhang HJ, Zhou J, Jia HT (2009) Induction of p14ARF by E2F1 contributes to 8-chloro-adenosine-induced apoptosis in human lung cancer H1299 cells. Chemotherapy 55:335–343PubMedGoogle Scholar
  279. 279.
    Nakamura K, Yoshikawa N, Yamaguchi Y, Kagota S, Shinozuka K, Kunitomo M (2006) Antitumor effect of cordycepin (3′-deoxyadenosine) on mouse melanoma and lung carcinoma cells involves adenosine A3 receptor stimulation. Anticancer Res 26:43–47PubMedGoogle Scholar
  280. 280.
    Kim SJ, Min HY, Chung HJ, Park EJ, Hong JY, Kang YJ, Shin DH, Jeong LS, Lee SK (2008) Inhibition of cell proliferation through cell cycle arrest and apoptosis by thio-Cl-IB-MECA, a novel A3 adenosine receptor agonist, in human lung cancer cells. Cancer Lett 264:309–315PubMedGoogle Scholar
  281. 281.
    Kamiya H, Kanno T, Fujita Y, Gotoh A, Nakano T, Nishizaki T (2012) Apoptosis-related gene transcription in human A549 lung cancer cells via A3 adenosine receptor. Cell Physiol Biochem 29:687–696PubMedGoogle Scholar
  282. 282.
    Kanno T, Nakano T, Fujita Y, Gotoh A, Nishizaki T (2012) Adenosine induces apoptosis in SBC-3 human lung cancer cells through A3 adenosine receptor-dependent AMID upregulation. Cell Physiol Biochem 30:666–677PubMedGoogle Scholar
  283. 283.
    Otsuki T, Kanno T, Fujita Y, Tabata C, Fukuoka K, Nakano T, Gotoh A, Nishizaki T (2012) A3 adenosine receptor-mediated p53-dependent apoptosis in Lu-65 human lung cancer cells. Cell Physiol Biochem 30:210–220PubMedGoogle Scholar
  284. 284.
    Block GJ, DiMattia GD, Prockop DJ (2010) Stanniocalcin-1 regulates extracellular ATP-induced calcium waves in human epithelial cancer cells by stimulating ATP release from bystander cells. PLoS One 5:e10237PubMedPubMedCentralGoogle Scholar
  285. 285.
    Zanini D, Schmatz R, Pimentel VC, Gutierres JM, Maldonado PA, Thomé GR, Cardoso AM, Stefanello N, Oliveira L, Chiesa J, Leal DB, Morsch VM, Schetinger MR (2012) Lung cancer alters the hydrolysis of nucleotides and nucleosides in platelets. Biomed Pharmacother 66:40–45PubMedGoogle Scholar
  286. 286.
    Inoue Y, Matsumoto H, Yamada S, Kawai K, Suemizu H, Gika M, Takanami I, Nakamura M, Iwazaki M (2010) ATP7B expression is associated with in vitro sensitivity to cisplatin in non-small cell lung cancer. Oncology Letters 1:279–282PubMedPubMedCentralGoogle Scholar
  287. 287.
    He QF, Wang LW, Mao JW, Sun XR, Li P, Zhong P, Nie SH, Jacob T, Chen LX (2004) Activation of chloride current and decrease of cell volume by ATP in nasopharyngeal carcinoma cells. Sheng Li Xue Bao 56:691–696PubMedGoogle Scholar
  288. 288.
    Yang L, Ye D, Ye W, Jiao C, Zhu L, Mao J, Jacob TJ, Wang L, Chen L (2011) ClC-3 is a main component of background chloride channels activated under isotonic conditions by autocrine ATP in nasopharyngeal carcinoma cells. J Cell Physiol 226:2516–2526PubMedGoogle Scholar
  289. 289.
    Bear CE, Li CH (1991) Calcium-permeable channels in rat hepatoma cells are activated by extracellular nucleotides. Am J Physiol 261:C1018–C1024PubMedGoogle Scholar
  290. 290.
    Fitz JG, Sostman AH (1994) Nucleotide receptors activate cation, potassium, and chloride currents in a liver cell line. Am J Physiol 266:G544–G553PubMedGoogle Scholar
  291. 291.
    Wu Y, Sun X, Imai M, Sultan B, Csizmadia E, Enjyoji K, Jackson S, Usheva A, Robson SC (2005) Modulation of RAS/ERK signaling by CD39/ENTPD1 during liver regeneration. Hepatology 42:Absr. 1138Google Scholar
  292. 292.
    Peres A, Giovannardi S (1995) Characteristics of the signal transduction system activated by ATP receptors in the hepatoma cell line N1S1-67. Biochim Biophys Acta 1265:33–39PubMedGoogle Scholar
  293. 293.
    Geschwind JF, Ko YH, Torbenson MS, Magee C, Pedersen PL (2002) Novel therapy for liver cancer: direct intraarterial injection of a potent inhibitor of ATP production. Cancer Res 62:3909–3913PubMedGoogle Scholar
  294. 294.
    Dolovcak S, Waldrop SL, Fitz JG, Kilic G (2009) 5-Nitro-2-(3-phenylpropylamino)benzoic acid (NPPB) stimulates cellular ATP release through exocytosis of ATP-enriched vesicles. J Biol Chem 284:33894–33903PubMedPubMedCentralGoogle Scholar
  295. 295.
    Speicher T, Foehrenbacher A, Pochic I, Weiland T, Wendel A (2010) Malignant but not naïve hepatocytes of human and rodent origin are killed by TNF after metabolic depletion of ATP by fructose. J Hepatol 53:896–902PubMedGoogle Scholar
  296. 296.
    Weiland T, Klein K, Zimmermann M, Speicher T, Venturelli S, Berger A, Bantel H, Königsrainer A, Schenk M, Weiss TS, Wendel A, Schwab M, Bitzer M, Lauer UM (2012) Selective protection of human liver tissue in TNF-targeting of cancers of the liver by transient depletion of adenosine triphosphate. PLoS One 7:e52496PubMedPubMedCentralGoogle Scholar
  297. 297.
    Lu CC, Yang JS, Huang AC, Hsia TC, Chou ST, Kuo CL, Lu HF, Lee TH, Wood WG, Chung JG (2010) Chrysophanol induces necrosis through the production of ROS and alteration of ATP levels in J5 human liver cancer cells. Mol Nutr Food Res 54:967–976PubMedPubMedCentralGoogle Scholar
  298. 298.
    Fujii T, Minagawa T, Shimizu T, Takeguchi N, Sakai H (2012) Inhibition of ecto-ATPase activity by curcumin in hepatocellular carcinoma HepG2 cells. J Physiol Sci 62:53–58PubMedGoogle Scholar
  299. 299.
    Espelt MV, Alberti GS, Chara O, Schwarzbaum PJ (2010) ATP induce ATP release in hepatoma cells. Purinergic Signal 6:S67Google Scholar
  300. 300.
    Frontini AV, De La Vega Elena CD, Nicolorich MV, Naves A, Schwarzbaum P, Venera GD (2011) In vivo effects of adenosine 5′-triphosphate on rat preneoplastic liver. Medicina (B Aires) 71:139–145Google Scholar
  301. 301.
    Hargrove JL, Granner DK (1982) Inhibition of hepatoma cell growth by analogs of adenosine and cyclic AMP and the influence of enzymes in mammalian sera. J Cell Physiol 111:232–238PubMedGoogle Scholar
  302. 302.
    Bar-Yehuda S, Stemmer SM, Madi L, Castel D, Ochaion A, Cohen S, Barer F, Zabutti A, Perez-Liz G, Del Valle L, Fishman P (2008) The A 3 adenosine receptor agonist CF102 induces apoptosis of hepatocellular carcinoma via de-regulation of the Wnt and NF-κB signal transduction pathways. Int J Oncol 33:287–295PubMedGoogle Scholar
  303. 303.
    Ohigashi T, Brookins J, Fisher JW (1993) Adenosine A 1 receptors and erythropoietin production. Am J Physiol 265:C934–C938PubMedGoogle Scholar
  304. 304.
    Wen LT, Knowles AF (2003) Extracellular ATP and adenosine induce cell apoptosis of human hepatoma Li-7A cells via the A3 adenosine receptor. Br J Pharmacol 140:1009–1018PubMedPubMedCentralGoogle Scholar
  305. 305.
    Cohen S, Stemmer SM, Zozulya G, Ochaion A, Patoka R, Barer F, Bar-Yehuda S, Rath-Wolfson L, Jacobson KA, Fishman P (2011) CF102 an A 3 adenosine receptor agonist mediates anti-tumor and anti-inflammatory effects in the liver. J Cell Physiol 226:2438–2447PubMedPubMedCentralGoogle Scholar
  306. 306.
    Stemmer S, Silverman MH, Kerns WD, Bar-Yehuda S, Fishman S, Harpaz Z, Farbstein M, Binyaminov O, Medalia G, Fishman P (2010) Phase 1/2 trial of CF102, a selective A3 adenosine receptor (A3AR) agonist, in patients with hepatocellular carcinoma (HCC). Eur J Cancer 8:122Google Scholar
  307. 307.
    Xiang HJ, Liu ZC, Wang DS, Chen Y, Yang YL, Dou KF (2006) Adenosine A2b receptor is highly expressed in human hepatocellular carcinoma. Hepatol Res 36:56–60PubMedGoogle Scholar
  308. 308.
    Sun X, Wu Y, Gao W, Enjyoji K, Csizmadia E, Müller CE, Murakami T, Robson SC (2010) CD39/ENTPD1 expression by CD4+ Foxp3+ regulatory T cells promotes hepatic metastatic tumor growth in mice. Gastroenterology 139:1030–1040PubMedPubMedCentralGoogle Scholar
  309. 309.
    Sun X, Han L, Seth P, Bian S, Li L, Csizmadia E, Junger WG, Schmelzle M, Usheva A, Tapper EB, Baffy G, Sukhatme VP, Wu Y, Robson SC (2013) Disordered purinergic signaling and abnormal cellular metabolism are associated with development of liver cancer in Cd39/ENTPD1 null mice. Hepatology 57:205–216PubMedGoogle Scholar
  310. 310.
    Hur H, Kim NK, Kim HG, Min BS, Lee KY, Shin SJ, Cheon JH, Choi SH (2012) Adenosine triphosphate-based chemotherapy response assay-guided chemotherapy in unresectable colorectal liver metastasis. Br J Cancer 106:53–60PubMedPubMedCentralGoogle Scholar
  311. 311.
    Borel F, Han R, Visser A, Petry H, van Deventer SJ, Jansen PL, Konstantinova P (2012) Adenosine triphosphate-binding cassette transporter genes up-regulation in untreated hepatocellular carcinoma is mediated by cellular microRNAs. Hepatology 55:821–832PubMedGoogle Scholar
  312. 312.
    Tzanakakis GN, Agarwal KC, Vezeridis MP (1993) Prevention of human pancreatic cancer cell-induced hepatic metastasis in nude mice by dipyridamole and its analog RA-233. Cancer 71:2466–2471PubMedGoogle Scholar
  313. 313.
    Verspohl EJ, Johannwille B, Waheed A, Neye H (2002) Effect of purinergic agonists and antagonists on insulin secretion from INS-1 cells (insulinoma cell line) and rat pancreatic islets. Can J Physiol Pharmacol 80:562–568PubMedGoogle Scholar
  314. 314.
    Szücs A, Demeter I, Burghardt B, Óvári G, Case RM, Steward MC, Varga G (2006) Vectorial bicarbonate transport by Capan-1 cells: a model for human pancreatic ductal secretion. Cell Physiol Biochem 18:253–264PubMedGoogle Scholar
  315. 315.
    Künzli BM, Berberat PO, Giese T, Csizmadia E, Kaczmarek E, Baker C, Halaceli I, Buchler MW, Friess H, Robson SC (2007) Upregulation of CD39/NTPDases and P2 receptors in human pancreatic disease. Am J Physiol Gastrointest Liver Physiol 292:G223–G230PubMedGoogle Scholar
  316. 316.
    Yamada T, Okajima F, Akbar M, Tomura H, Narita T, Yamada T, Ohwada S, Morishita Y, Kondo Y (2002) Cell cycle arrest and the induction of apoptosis in pancreatic cancer cells exposed to adenosine triphosphate in vitro. Oncol Rep 9:113–117PubMedGoogle Scholar
  317. 317.
    Chow JY, Shim KN, Ornelas TA, Carethers JM, Dong H (2009) Purinergic P2y2 receptor and Ca2+-mediated proliferation of human pancreatic epithelial cancer cells. Gastroenterology 136:A312Google Scholar
  318. 318.
    Kang CM, Kim H, Cho Y, Kim YS, Hwang HK, Choi HJ, Lee WJ (2012) In vitro adenosine triphosphate-based chemotherapy response assay (ATP-CRA) in solid pseudopapillary tumor of the pancreas. Pancreas 41:498–500PubMedGoogle Scholar
  319. 319.
    Kozlow W, Guise TA (2005) Breast cancer metastasis to bone: mechanisms of osteolysis and implications for therapy. J Mammary Gland Biol Neoplasia 10:169–180PubMedGoogle Scholar
  320. 320.
    Kakonen SM, Mundy GR (2003) Mechanisms of osteolytic bone metastases in breast carcinoma. Cancer 97:834–839PubMedGoogle Scholar
  321. 321.
    Uluçkan Ö, Eagleton MC, Floyd DH, Morgan EA, Hirbe AC, Kramer M, Dowland N, Prior JL, Piwnica-Worms D, Jeong SS, Chen R, Weilbaecher K (2008) APT102, a novel adpase, cooperates with aspirin to disrupt bone metastasis in mice. J Cell Biochem 104:1311–1323PubMedPubMedCentralGoogle Scholar
  322. 322.
    Gouin-Thibault I, Achkar A, Samama MM (2001) The thrombophilic state in cancer patients. Acta Haematol 106:33–42PubMedGoogle Scholar
  323. 323.
    Boissier S, Magnetto S, Frappart L, Cuzin B, Ebetino FH, Delmas PD, Clezardin P (1997) Bisphosphonates inhibit prostate and breast carcinoma cell adhesion to unmineralized and mineralized bone extracellular matrices. Cancer Res 57:3890–3894PubMedGoogle Scholar
  324. 324.
    Mönkkönen H, Kuokkanen J, Holen I, Evans A, Lefley DV, Jauhiainen M, Auriola S, Mönkkönen J (2008) Bisphosphonate-induced ATP analog formation and its effect on inhibition of cancer cell growth. Anticancer Drugs 19:391–399PubMedGoogle Scholar
  325. 325.
    Korcok J, Raimundo LN, Ke HZ, Sims SM, Dixon SJ (2004) Extracellular nucleotides act through P2X7 receptors to activate NF-kappaB in osteoclasts. J Bone Miner Res 19:642–651PubMedGoogle Scholar
  326. 326.
    Leto G, Sepporta MV, Crescimanno M, Flandina C, Tumminello FM (2010) Cathepsin L in metastatic bone disease: therapeutic implications. Biol Chem 391:655–664PubMedGoogle Scholar
  327. 327.
    Shafat I, Vlodavsky I, Ilan N (2006) Characterization of mechanisms involved in secretion of active heparanase. J Biol Chem 281:23804–23811PubMedGoogle Scholar
  328. 328.
    Hoebertz A, Arnett TR, Burnstock G (2003) Regulation of bone resorption and formation by purines and pyrimidines. Trends Pharmacol Sci 24:290–297PubMedGoogle Scholar
  329. 329.
    Kumagai H, Sacktor B, Filburn CR (1991) Purinergic regulation of cytosolic calcium and phosphoinositide metabolism in rat osteoblast-like osteosarcoma cells. J Bone Miner Res 6:697–708PubMedGoogle Scholar
  330. 330.
    Reimer WJ, Dixon SJ (1992) Extracellular nucleotides elevate [Ca2+]i in rat osteoblastic cells by interaction with two receptor subtypes. Am J Physiol 263:C1040–C1048PubMedGoogle Scholar
  331. 331.
    Schöfl C, Cuthbertson KS, Walsh CA, Mayne C, Cobbold P, von zur Mühlen A, Hesch RD, Gallagher JA (1992) Evidence for P2-purinoceptors on human osteoblast-like cells. J Bone Miner Res 7:485–491PubMedGoogle Scholar
  332. 332.
    Bowler WB, Birch MA, Gallagher JA, Bilbe G (1995) Identification and cloning of human P2U purinoceptor present in osteoclastoma, bone, and osteoblasts. J Bone Miner Res 10:1137–1145PubMedGoogle Scholar
  333. 333.
    Katz S, Bilbao PS, Boland RL, Santillán G (2006) Modulation of intracellular calcium and MAPK activation by ATP in osteoblasts and breat cancer cells. J Bone Mineral Res 21:S390Google Scholar
  334. 334.
    Liu PS, Chen CY (2010) Butyl benzyl phthalate suppresses the ATP-induced cell proliferation in human osteosarcoma HOS cells. Toxicol Appl Pharmacol 244:308–314PubMedGoogle Scholar
  335. 335.
    Shah K, Patel V, Wang N, Gartland A (2010) The effect of ATP on cancer cell proliferation in vitro—involvement of multiple P2X receptors. Purinergic Signal 6:140Google Scholar
  336. 336.
    Krett NL, Davies KM, Ayres M, Ma C, Nabhan C, Gandhi V, Rosen ST (2004) 8-Amino-adenosine is a potential therapeutic agent for multiple myeloma. Mol Cancer Ther 3:1411–1420PubMedGoogle Scholar
  337. 337.
    Farrell AW, Gadeock S, Pupovac A, Wang B, Jalilian I, Ranson M, Sluyter R (2010) P2X7 receptor activation induces cell death and CD23 shedding in human RPMI 8226 multiple myeloma cells. Biochim Biophys Acta 1800:1173–1182PubMedGoogle Scholar
  338. 338.
    Rickles RJ, Tam WF, Giordano TP III, Pierce LT, Farwell M, McMillin DW, Necheva A, Crowe D, Chen M, Avery W, Kansra V, Nawrocki ST, Carew JS, Giles FJ, Mitsiades CS, Borisy AA, Anderson KC, Lee MS (2012) Adenosine A2A and beta-2 adrenergic receptor agonists: novel selective and synergistic multiple myeloma targets discovered through systematic combination screening. Mol Cancer Ther 11:1432–1442PubMedGoogle Scholar
  339. 339.
    Cervantes-Gomez F, Nimmanapalli R, Gandhi V (2011) ATP analog enhances the actions of a heat shock protein 90 inhibitor in multiple myeloma cells. J Pharmacol Exp Ther 339:545–554PubMedPubMedCentralGoogle Scholar
  340. 340.
    Froio J, Abraham EH, Soni R, Epstein A, Okunieff P (1995) Effect of intraperitoneal ATP on tumor growth and bone marrow radiation tolerance. Acta Oncol 34:419–422PubMedGoogle Scholar
  341. 341.
    Chizhmakov I, Mamenko N, Volkova T, Khasabova I, Simone DA, Krishtal O (2009) P2X receptors in sensory neurons co-cultured with cancer cells exhibit a decrease in opioid sensitivity. Eur J Neurosci 29:76–86PubMedGoogle Scholar
  342. 342.
    Nejime N, Kagota S, Tada Y, Nakamura K, Hashimoto M, Kunitomo M, Shinozuka K (2009) Possible participation of chloride ion channels in ATP release from cancer cells in suspension. Clin Exp Pharmacol Physiol 36:278–282PubMedGoogle Scholar
  343. 343.
    Dubyak GR (2012) Function without form: an ongoing search for maxi-anion channel proteins. Focus on “Maxi-anion channel and pannexin 1 hemichannel constitute separate pathways for swelling-induced ATP release in murine L929 fibrosarcoma cells”. Am J Physiol Cell Physiol 303:C913–C915PubMedPubMedCentralGoogle Scholar
  344. 344.
    Islam MR, Uramoto H, Okada T, Sabirov RZ, Okada Y (2012) Maxi-anion channel and pannexin 1 hemichannel constitute separate pathways for swelling-induced ATP release in murine L929 fibrosarcoma cells. Am J Physiol Cell Physiol 303:C924–C935PubMedGoogle Scholar
  345. 345.
    Hoferová Z, Hofer M, Pospíšil M, Znojil V, Chramostová K (2003) Effects of synthetic adenosine receptor agonosts on growth characteristics of murine G:5:113 fibrosarcoma cells in vitro. Drug Dev Res 60:303–311Google Scholar
  346. 346.
    Mercadante S (1997) Malignant bone pain: pathophysiology and treatment. Pain 69:1–18PubMedGoogle Scholar
  347. 347.
    Caraceni A, Portenoy RK (1999) An international survey of cancer pain characteristics and syndromes. IASP Task Force on Cancer Pain. International Association for the Study of Pain. Pain 82:263–274PubMedGoogle Scholar
  348. 348.
    Coleman R (1997) Management of bone metastases. Cancer Treat Rev 23(Suppl 1):S69–S75PubMedGoogle Scholar
  349. 349.
    Delaney A, Fleetwood-Walker SM, Colvin LA, Fallon M (2008) Translational medicine: cancer pain mechanisms and management. Br J Anaesth 101:87–94PubMedGoogle Scholar
  350. 350.
    Burnstock G (1996) A unifying purinergic hypothesis for the initiation of pain. Lancet 347:1604–1605PubMedGoogle Scholar
  351. 351.
    Wirkner K, Sperlagh B, Illes P (2007) P2X3 receptor involvement in pain states. Mol Neurobiol 36:165–183PubMedGoogle Scholar
  352. 352.
    Chen CC, Akopian AN, Sivilotti L, Colquhoun D, Burnstock G, Wood JN (1995) A P2X purinoceptor expressed by a subset of sensory neurons. Nature 377:428–431PubMedGoogle Scholar
  353. 353.
    Bradbury EJ, Burnstock G, McMahon SB (1998) The expression of P2X3 purinoceptors in sensory neurons: effects of axotomy and glial-derived neurotrophic factor. Mol Cell Neurosci 12:256–268PubMedGoogle Scholar
  354. 354.
    Gilchrist LS, Cain DM, Harding-Rose C, Kov AN, Wendelschafer-Crabb G, Kennedy WR, Simone DA (2005) Re-organization of P2X3 receptor localization on epidermal nerve fibers in a murine model of cancer pain. Brain Res 1044:197–205PubMedGoogle Scholar
  355. 355.
    Kakimoto S, Nagakura Y, Tamura S, Watabiki T, Shibasaki K, Tanaka S, Mori M, Sasamata M, Okada M (2008) Minodronic acid, a third-generation bisphosphonate, antagonizes purinergic P2X2/3 receptor function and exerts an analgesic effect in pain models. Eur J Pharmacol 589:98–101PubMedGoogle Scholar
  356. 356.
    Park HC, Seong J, An JH, Kim J, Kim UJ, Lee BW (2005) Alteration of cancer pain-related signals by radiation: proteomic analysis in an animal model with cancer bone invasion. Int J Radiat Oncol Biol Phys 61:1523–1534PubMedGoogle Scholar
  357. 357.
    Schöfl C, Rössig L, Mader T, Börger J, Pötter E, von zur Mühlen A, Brabant G (1997) Impairment of ATP-induced Ca2+-signalling in human thyroid cancer cells. Mol Cell Endocrinol 133:33–39PubMedGoogle Scholar
  358. 358.
    Pines A, Perrone L, Bivi N, Romanello M, Damante G, Gulisano M, Kelley MR, Quadrifoglio F, Tell G (2005) Activation of APE1/Ref-1 is dependent on reactive oxygen species generated after purinergic receptor stimulation by ATP. Nucleic Acids Res 33:4379–4394PubMedPubMedCentralGoogle Scholar
  359. 359.
    Pines A, Bivi N, Vascotto C, Romanello M, D’Ambrosio C, Scaloni A, Damante G, Morisi R, Filetti S, Ferretti E, Quadrifoglio F, Tell G (2006) Nucleotide receptors stimulation by extracellular ATP controls Hsp90 expression through APE1/Ref-1 in thyroid cancer cells: a novel tumorigenic pathway. J Cell Physiol 209:44–55PubMedGoogle Scholar
  360. 360.
    Caraccio N, Monzani F, Santini E, Cuccato S, Ferrari D, Callegari MG, Gulinelli S, Pizzirani C, Di Virgilio F, Ferrannini E, Solini A (2005) Extracellular adenosine 5′-triphosphate modulates interleukin-6 production by human thyrocytes through functional purinergic P2 receptors. Endocrinology 146:3172–3178PubMedGoogle Scholar
  361. 361.
    Solini A, Cuccato S, Ferrari D, Santini E, Gulinelli S, Callegari MG, Dardano A, Faviana P, Madec S, Di Virgilio F, Monzani F (2008) Increased P2X7 receptor expression and function in thyroid papillary cancer: a new potential marker of the disease? Endocrinology 149:389–396PubMedGoogle Scholar
  362. 362.
    Dardano A, Falzoni S, Caraccio N, Polini A, Tognini S, Solini A, Berti P, Di Virgilio F, Monzani F (2009) 1513A>C polymorphism in the P2X7 receptor gene in patients with papillary thyroid cancer: correlation with histological variants and clinical parameters. J Clin Endocrinol Metab 94:695–698PubMedGoogle Scholar
  363. 363.
    Gu LQ, Li FY, Zhao L, Liu Y, Chu Q, Zang XX, Liu JM, Ning G, Zhao YJ (2010) Association of XIAP and P2X7 receptor expression with lymph node metastasis in papillary thyroid carcinoma. Endocrine 38:276–282PubMedGoogle Scholar
  364. 364.
    Lobo GP, Waite KA, Planchon SM, Romigh T, Houghton JA, Eng C (2008) ATP modulates PTEN subcellular localization in multiple cancer cell lines. Hum Mol Genet 17:2877–2885PubMedPubMedCentralGoogle Scholar
  365. 365.
    Yang DM, Teng HC, Chen KH, Tsai ML, Lee TK, Chou YC, Chi CW, Chiou SH, Lee CH (2009) Clodronate-induced cell apoptosis in human thyroid carcinoma is mediated via the P2 receptor signaling pathway. J Pharmacol Exp Ther 330:613–623PubMedGoogle Scholar
  366. 366.
    Robinson-White AJ, Hsiao HP, Leitner WW, Greene E, Bauer A, Krett NL, Nesterova M, Stratakis CA (2008) Protein kinase A-independent inhibition of proliferation and induction of apoptosis in human thyroid cancer cells by 8-Cl-adenosine. J Clin Endocrinol Metab 93:1020–1029PubMedPubMedCentralGoogle Scholar
  367. 367.
    Morello S, Petrella A, Festa M, Popolo A, Monaco M, Vuttariello E, Chiappetta G, Parente L, Pinto A (2008) Cl-IB-MECA inhibits human thyroid cancer cell proliferation independently of A3 adenosine receptor activation. Cancer Biol Ther 7:278–284PubMedGoogle Scholar
  368. 368.
    Kondo T, Nakazawa T, Kawasaki T, Mochizuki K, Niu DF, Yamane T, Katoh R (2011) Expression of adenosine receptors in thyroid carcenoma. Mod Pathol 24:137AGoogle Scholar
  369. 369.
    Ruzsnavszky O, Telek A, Gönczi M, Balogh A, Remenyik E, Csernoch L (2011) UV-B induced alteration in purinergic receptors and signaling on HaCaT keratinocytes. J Photochem Photobiol B 105:113–118PubMedGoogle Scholar
  370. 370.
    Klein E, Burgess GH, Bloch A, Milgrom H, Holtermann OA (1975) The effects of nucleoside analogs on cutaneous neoplasms. Ann N Y Acad Sci 255:216–224PubMedGoogle Scholar
  371. 371.
    Hosoi K, Edidin M (1989) Exogenous ATP and other nucleoside phosphates modulate epidermal growth factor receptors of A-431 epidermoid carcinoma cells. Proc Natl Acad Sci U S A 86:4510–4514PubMedPubMedCentralGoogle Scholar
  372. 372.
    Gonzalez FA, Alfonzo RG, Toro JR, Heppel LA (1989) Receptor specific for certain nucleotides stimulates inositol phosphate metabolism and Ca2+ fluxes in A431 cells. J Cell Physiol 141:606–617PubMedGoogle Scholar
  373. 373.
    Hosoi K, Fujishita M, Sugita K, Kurihara K, Atsumi T, Murai T, Ueha T (1992) P2 purinergic receptors and cellular calcium metabolism in A 431 human epidermoid carcinoma cells. Am J Physiol 262:C635–C643PubMedGoogle Scholar
  374. 374.
    Sugita K, Kurihara K, Hosoi K, Atsumi T, Takahashi T, Kohno M, Ueha T (1994) Effects of pertussis toxin on signal transductions via P2-purinergic receptors in A-431 human epidermoidal carcinoma cells. Enzyme Protein 48:222–228PubMedGoogle Scholar
  375. 375.
    Correale P, Giuliano M, Tagliaferri P, Guarrasi R, Caraglia M, Marinetti MR, Iezzi T, Bianco AR, Procopio A (1995) Role of adenosine 5′ triphosphate in lymphokine activated (LAK) killing of human tumor cells. Res Commun Mol Pathol Pharmacol 87:67–69Google Scholar
  376. 376.
    Völkl T, Ogilvie A, Neuhuber W, Ogilvie A (2008) Cell death induced by uridine 5′-triphosphate (UTP) in contrast to adenosine 5′-triphosphate (ATP) in human epidermoid carcinoma cells (A-431). Cell Physiol Biochem 22:441–454PubMedGoogle Scholar
  377. 377.
    Fu W, McCormick T, Qi X, Luo L, Zhou L, Li X, Wang BC, Gibbons HE, Abdul-Karim FW, Gorodeski GI (2009) Activation of P2X7-mediated apoptosis inhibits DMBA/TPA-induced formation of skin papillomas and cancer in mice. BMC Cancer 9:114PubMedPubMedCentralGoogle Scholar
  378. 378.
    Hsu WL, Tsai MH, Lin MW, Chiu YC, Lu JH, Chang CH, Yu HS, Yoshioka T (2012) Differential effects of arsenic on calcium signaling in primary keratinocytes and malignant (HSC-1) cells. Cell Calcium 52:161–169PubMedGoogle Scholar
  379. 379.
    Rai B, Kaur J, Jacobs R, Anand SC (2011) Adenosine deaminase in saliva as a diagnostic marker of squamous cell carcinoma of tongue. Clin Oral Investig 15:347–349PubMedGoogle Scholar
  380. 380.
    Kitagawa T, Amano F, Akamatsu Y (1988) External ATP-induced passive permeability change and cell lysis of cultured transformed cells: action in serum-containing growth media. Biochim Biophys Acta 941:257–263PubMedGoogle Scholar
  381. 381.
    Mure T, Sano K, Kitagawa T (1992) Modulation of membrane permeability, cell proliferation and cytotoxicity of antitumor agents by external ATP in mouse tumor cells. Jpn J Cancer Res 83:121–126PubMedGoogle Scholar
  382. 382.
    Kuhnle GE, Dellian M, Walenta S, Mueller-Klieser W, Goetz AE (1992) Simultaneous high-resolution measurement of adenosine triphosphate levels and blood flow in the hamster amelanotic melanoma A-Mel-3. J Natl Cancer Inst 84:1642–1647PubMedGoogle Scholar
  383. 383.
    Walenta S, Dellian M, Goetz AE, Kuhnle GE, Mueller-Klieser W (1992) Pixel-to-pixel correlation between images of absolute ATP concentrations and blood flow in tumours. Br J Cancer 66:1099–1102PubMedPubMedCentralGoogle Scholar
  384. 384.
    Dzhandzhugazyan KN, Kirkin AF, P t S, Zeuthen J (1998) Ecto-ATP diphosphohydrolase/CD39 is overexpressed in differentiated human melanomas. FEBS Lett 430:227–230PubMedGoogle Scholar
  385. 385.
    Palomares T, Bilbao P, del Olmo M, Castro B, Calle Y, Alonso-Varona A (1999) In vitro and in vivo comparison between the effects of treatment with adenosine triphosphate and treatment with buthionine sulfoximine on chemosensitization and tumour growth of B16 melanoma. Melanoma Res 9:233–242PubMedGoogle Scholar
  386. 386.
    Slater M, Scolyer RA, Gidley-Baird A, Thompson JF, Barden JA (2003) Increased expression of apoptotic markers in melanoma. Melanoma Res 13:137–145PubMedGoogle Scholar
  387. 387.
    Tsukimoto M, Ohshima Y, Harada H, Takenouchi T, Sato M, Suzuki A, Kitani H, Kojima S (2008) Over-expression of P2X7 receptor enhances tumor growth in vivo, but not in vitro. Purinergic Signalling 4:S150–S151Google Scholar
  388. 388.
    Hattori F, Ohshima Y, Seki S, Tsukimoto M, Sato M, Takenouchi T, Suzuki A, Takai E, Kitani H, Harada H, Kojima S (2012) Feasibility study of B16 melanoma therapy using oxidized ATP to target purinergic receptor P2X7. Eur J Pharmacol 695:20–26PubMedGoogle Scholar
  389. 389.
    Deli T, Varga N, Ádám A, Kenessey I, Ráasó E, Puskás LG, Tóovári J, Fodor J, Fehér M, Szigeti GP, Csernoch L, Tímár J (2007) Functional genomics of calcium channels in human melanoma cells. Int J Cancer 121:55–65PubMedGoogle Scholar
  390. 390.
    Kretz M, Ring S, Mahnke K (2009) ATP release by B16 melanomas upregulate the expression of the ectonucleotidase CD39 on Treg. J Invest Dermatol 129:S4Google Scholar
  391. 391.
    Ring S, Enk A, Mahnke K (2011) A role for adenosine triphosphate in regulating immune responses during melanoma growth. J Invest Dermatol 131:S91Google Scholar
  392. 392.
    Fishman P, Bar-Yehuda S (1998) Extracellular adenosine acts as a chemoprotective agent. Proc Am Assoc Cancer Res 39:3196Google Scholar
  393. 393.
    Woodhouse EC, Amanatullah DF, Schetz JA, Liotta LA, Stracke ML, Clair T (1998) Adenosine receptor mediates motility in human melanoma cells. Biochem Biophys Res Commun 246:888–894PubMedGoogle Scholar
  394. 394.
    Merighi S, Varani K, Gessi S, Cattabriga E, Iannotta V, Ulouglu C, Leung E, Borea PA (2001) Pharmacological and biochemical characterization of adenosine receptors in the human malignant melanoma A375 cell line. Br J Pharmacol 134:1215–1226PubMedPubMedCentralGoogle Scholar
  395. 395.
    Merighi S, Mirandola P, Milani D, Varani K, Gessi S, Klotz KN, Leung E, Baraldi PG, Borea PA (2002) Adenosine receptors as mediators of both cell proliferation and cell death of cultured human melanoma cells. J Invest Dermatol 119:923–933PubMedGoogle Scholar
  396. 396.
    Madi L, Bar-Yehuda S, Barer F, Ardon E, Ochaion A, Fishman P (2003) A3 adenosine receptor activation in melanoma cells: association between receptor fate and tumor growth inhibition. J Biol Chem 278:42121–42130PubMedGoogle Scholar
  397. 397.
    Merighi S, Benini A, Mirandola P, Gessi S, Varani K, Leung E, Maclennan S, Baraldi PG, Borea PA (2005) A3 adenosine receptors modulate hypoxia-inducible factor-1α expression in human A375 melanoma cells. Neoplasia 7:894–903PubMedPubMedCentralGoogle Scholar
  398. 398.
    Morello S, Sorrentino R, Montinaro A, Luciano A, Maiolino P, Ngkelo A, Arra C, Adcock IM, Pinto A (2011) NK1.1+ cells and CD8+ T cells mediate the antitumor activity of Cl-IB-MECA in a mouse melanoma model. Neoplasia 13:365–373PubMedPubMedCentralGoogle Scholar
  399. 399.
    Soares AF, Diniz C, Fresco P (2012) A3-adenosine receptor effects on malignant melanoma cells. FEBS J 279:547Google Scholar
  400. 400.
    Merighi S, Baraldi PG, Gessi S, Iannotta V, Klotz JN, Leung E, Mirandola P, Tabrizi MA, Varani K, Borea PA (2003) Adenosine receptors and human melanoma. Drug Dev Res 58:377–385Google Scholar
  401. 401.
    Merighi S, Simioni C, Gessi S, Varani K, Mirandola P, Tabrizi MA, Baraldi PG, Borea PA (2009) A2B and A3 adenosine receptors modulate vascular endothelial growth factor and interleukin-8 expression in human melanoma cells treated with etoposide and doxorubicin. Neoplasia 11:1064–1073PubMedPubMedCentralGoogle Scholar
  402. 402.
    Raskovalova T, Lokshin A, Huang X, Su Y, Mandic M, Zarour HM, Jackson EK, Gorelik E (2007) Inhibition of cytokine production and cytotoxic activity of human antimelanoma specific CD8+ and CD4+ T lymphocytes by adenosine-protein kinase A type I signaling. Cancer Res 67:5949–5956PubMedGoogle Scholar
  403. 403.
    Urunsak IF, Gulec UK, Paydas S, Seydaoglu G, Guzel AB, Vardar MA (2012) Adenosine deaminase activity in patients with ovarian neoplasms. Arch Gynecol Obstet 286:155–159PubMedGoogle Scholar
  404. 404.
    Aiton JF, Lamb JF (1980) The effect of exogenous adenosine triphosphate on potassium movements in HeLa cells. Q J Exp Physiol Cogn Med Sci 65:47–62PubMedGoogle Scholar
  405. 405.
    Smit MJ, Leurs R, Bloemers SM, Tertoolen LG, Bast A, De Laat SW, Timmerman H (1993) Extracellular ATP elevates cytoplasmatic free Ca2+ in HeLa cells by the interaction with a 5′-nucleotide receptor. Eur J Pharmacol 247:223–226PubMedGoogle Scholar
  406. 406.
    Muscella A, Elia MG, Greco S, Storelli C, Marsigliante S (2003) Activation of P2Y2 purinoceptor inhibits the activity of the Na+/K+-ATPase in HeLa cells. Cell Signal 15:115–121PubMedGoogle Scholar
  407. 407.
    Okuda A, Furuya K, Kiyohara T (2003) ATP-induced calcium oscillations and change of P2Y subtypes with culture conditions in HeLa cells. Cell Biochem Funct 21:61–68PubMedGoogle Scholar
  408. 408.
    Muscella A, Greco S, Elia MG, Storelli C, Marsigliante S (2004) Differential signalling of purinoceptors in HeLa cells through the extracellular signal-regulated kinase and protein kinase C pathways. J Cell Physiol 200:428–439PubMedGoogle Scholar
  409. 409.
    Feng YH, Li X, Wang L, Zhou L, Gorodeski GI (2006) A truncated P2X7 receptor variant (P2X7-j) endogenously expressed in cervical cancer cells antagonizes the full-length P2X7 receptor through hetero-oligomerization. J Biol Chem 281:17228–17237PubMedPubMedCentralGoogle Scholar
  410. 410.
    Lee SG, Choi JK, Choi BH, Lim Y, Kim YH, Lee KH, Shin JC, Ahn WS (2006) The effect of adenosine 5′-triphosphate on calcium mobilization and cell proliferation in cervical cancer cells. Eur J Obstet Gynecol Reprod Biol 127:110–114PubMedGoogle Scholar
  411. 411.
    Tam KF, Ng TY, Liu SS, Tsang PC, Kwong PW, Ngan HY (2005) Potential application of the ATP cell viability assay in the measurement of intrinsic radiosensitivity in cervical cancer. Gynecol Oncol 96:765–770PubMedGoogle Scholar
  412. 412.
    Buvinic S, Bravo-Zehnder M, Boyer JL, Huidobro-Toro JP, González A (2007) Nucleotide P2Y1 receptor regulates EGF receptor mitogenic signaling and expression in epithelial cells. J Cell Sci 120:4289–4301PubMedGoogle Scholar
  413. 413.
    Hopfe M, Henrich B (2008) OppA, the ecto-ATPase of Mycoplasma hominis induces ATP release and cell death in HeLa cells. BMC Microbiol 8:55PubMedPubMedCentralGoogle Scholar
  414. 414.
    Liang WG, Su CC, Nian JH, Chiang AS, Li SY, Yang JJ (2011) Human connexin30.2/31.3 (GJC3) does not form functional gap junction channels but causes enhanced ATP release in HeLa cells. Cell Biochem Biophys 61:189–197PubMedGoogle Scholar
  415. 415.
    Huidobro-Toro JP, Lopez J, Hinojosa A, Buvinic S, Gonzalez A (2010) ATP released and autocrine signalling following gentle pipetting of HeLa cell medium. Purinergic Signal 6:S70Google Scholar
  416. 416.
    Maldonado PA, Pimentel VC, Negrini LA, Morsch VM, Schetinger MR (2012) Role of the purinergic system in patients with cervical intraepithelial neoplasia and uterine cancer. Biomed Pharmacother 66:6–11PubMedGoogle Scholar
  417. 417.
    Popper LD, Batra S (1993) Calcium mobilization and cell proliferation activated by extracellular ATP in human ovarian tumour cells. Cell Calcium 14:209–218PubMedGoogle Scholar
  418. 418.
    Batra S, Fadeel I (1994) Release of intracellular calcium and stimulation of cell growth by ATP and histamine in human ovarian cancer cells (SKOV-3). Cancer Lett 77:57–63PubMedGoogle Scholar
  419. 419.
    Maymon R, Bar-Shira MB, Cohen-Armon M, Holtzinger M, Leibovici J (1994) Enhancing effect of ATP on intracellular adriamycin penetration in human ovarian cancer cell lines. Biochim Biophys Acta 1201:173–178PubMedGoogle Scholar
  420. 420.
    Schultze-Mosgau A, Katzur AC, Arora KK, Stojilkovic SS, Diedrich K, Ortmann O (2000) Characterization of calcium-mobilizing, purinergic P2Y2 receptors in human ovarian cancer cells. Mol Hum Reprod 6:435–442PubMedGoogle Scholar
  421. 421.
    Konecny G, Crohns C, Pegram M, Felber M, Lude S, Kurbacher C, Cree IA, Hepp H, Untch M (2000) Correlation of drug response with the ATP tumorchemosensitivity assay in primary FIGO stage III ovarian cancer. Gynecol Oncol 77:258–263PubMedGoogle Scholar
  422. 422.
    Ng TY, Ngan HY, Cheng DK, Wong LC (2000) Clinical applicability of the ATP cell viability assay as a predictor of chemoresponse in platinum-resistant epithelial ovarian cancer using nonsurgical tumor cell samples. Gynecol Oncol 76:405–408PubMedGoogle Scholar
  423. 423.
    O’Meara AT, Sevin BU (2001) Predictive value of the ATP chemosensitivity assay in epithelial ovarian cancer. Gynecol Oncol 83:334–342PubMedGoogle Scholar
  424. 424.
    Cree IA, Kurbacher CM, Lamont A, Hindley AC, Love S (2007) A prospective randomized controlled trial of tumour chemosensitivity assay directed chemotherapy versus physician’s choice in patients with recurrent platinum-resistant ovarian cancer. Anticancer Drugs 18:1093–1101PubMedGoogle Scholar
  425. 425.
    Neubauer H, Stefanova M, Solomayer E, Meisner C, Zwirner M, Wallwiener D, Fehm T (2008) Predicting resistance to platinum-containing chemotherapy with the ATP tumor chemosensitivity assay in primary ovarian cancer. Anticancer Res 28:949–955PubMedGoogle Scholar
  426. 426.
    Glaysher S, Gabriel FG, Johnson P, Polak M, Knight LA, Parker K, Poole M, Narayanan A, Cree IA (2010) Molecular basis of chemosensitivity of platinum pre-treated ovarian cancer to chemotherapy. Br J Cancer 103:656–662PubMedPubMedCentralGoogle Scholar
  427. 427.
    Knight LA, Kurbacher CM, Glaysher S, Fernando A, Reichelt R, Dexel S, Reinhold U, Cree IA (2009) Activity of mevalonate pathway inhibitors against breast and ovarian cancers in the ATP-based tumour chemosensitivity assay. BMC Cancer 9:38PubMedPubMedCentralGoogle Scholar
  428. 428.
    Barcz E, Sommer E, Janik P, Marianowski L, Skopinska-Rozewska E (2000) Adenosine receptor antagonism causes inhibition of angiogenic activity of human ovarian cancer cells. Oncol Rep 7:1285–1291PubMedGoogle Scholar
  429. 429.
    Song H, Ramus SJ, Shadforth D, Quaye L, Kjaer SK, Dicioccio RA, Dunning AM, Hogdall E, Hogdall C, Whittemore AS, McGuire V, Lesueur F, Easton DF, Jacobs IJ, Ponder BA, Gayther SA, Pharoah PD (2006) Common variants in RB1 gene and risk of invasive ovarian cancer. Cancer Res 66:10220–10226PubMedGoogle Scholar
  430. 430.
    Rotte A, Garmann D, Buss I, Jaehde U (2010) Effect of extracellular ATP on cisplatin-induced cytotoxicity in human ovarian carcinoma cells. Chemotherapy 56:1–8PubMedGoogle Scholar
  431. 431.
    Katzur AC, Koshimizu T, Tomic M, Schultze-Mosgau A, Ortmann O, Stojilkovic SS (1999) Expression and responsiveness of P2Y2 receptors in human endometrial cancer cell lines. J Clin Endocrinol Metab 84:4085–4091PubMedGoogle Scholar
  432. 432.
    Aida T, Takebayashi Y, Shimizu T, Okamura C, Higasimoto M, Kanzaki A, Nakayama K, Terada K, Sugiyama T, Miyazaki K, Ito K, Takenoshita S, Yaegashi N (2005) Expression of copper-transporting P-type adenosine triphosphatase (ATP7B) as a prognostic factor in human endometrial carcinoma. Gynecol Oncol 97:41–45PubMedGoogle Scholar
  433. 433.
    Li X, Zhou L, Feng YH, Abdul-Karim FW, Gorodeski GI (2006) The P2X7 receptor: a novel biomarker of uterine epithelial cancers. Cancer Epidemiol Biomarkers Prev 15:1906–1913PubMedPubMedCentralGoogle Scholar
  434. 434.
    Li X, Qi X, Zhou L, Catera D, Rote NS, Potashkin J, Abdul-Karim FW, Gorodeski GI (2007) Decreased expression of P2X7 in endometrial epithelial pre-cancerous and cancer cells. Gynecol Oncol 106:233–243PubMedPubMedCentralGoogle Scholar
  435. 435.
    Zhou L, Qi X, Potashkin JA, Abdul-Karim FW, Gorodeski GI (2008) MicroRNAs miR-186 and miR-150 down-regulate expression of the pro-apoptotic purinergic P2X7 receptor by activation of instability sites at the 3′-untranslated region of the gene that decrease steady-state levels of the transcript. J Biol Chem 283:28274–28286PubMedPubMedCentralGoogle Scholar
  436. 436.
    Tam KF, Ng TY, Tsang PC, Li CF, Ngan HY (2006) Potential use of the adenosine triphosphate cell viability assay in endometrial cancer. J Soc Gynecol Investig 13:518–522PubMedGoogle Scholar
  437. 437.
    Boabang P, Kurbacher CM, Kohlhagen H, Waida A, Amo-Takyi BK (2000) Anti-neoplastic activity of topotecan versus cisplatin, etoposide and paclitaxel in four squamous cell cancer cell lines of the female genital tract using an ATP-tumor chemosensitivity assay. Anticancer Drugs 11:843–848PubMedGoogle Scholar
  438. 438.
    Acosta Maldonado P, de Carvalho CM, Vargas Becker L, Flores C, Beatriz Moretto M, Morsch V, Chitolina Schetinger MR (2008) Ectonucleotide pyrophosphatase/phosphodiesterase (E-NPP) and adenosine deaminase (ADA) activities in patients with uterine cervix neoplasia. Clin Biochem 41:400–406PubMedGoogle Scholar
  439. 439.
    Sylwestrowicz TA, Ma DD, Murphy PP, Massaia M, Prentice HG, Hoffbrand AV, Greaves MF (1982) 5′nucleotidase, adenosine deaminase and purine nucleoside phosphorylase activities in acute leukaemia. Leuk Res 6:475–482PubMedGoogle Scholar
  440. 440.
    Seifert R, Burde R, Schultz G (1989) Activation of NADPH oxidase by purine and pyrimidine nucleotides involves G proteins and is potentiated by chemotactic peptides. Biochem J 259:813–819PubMedPubMedCentralGoogle Scholar
  441. 441.
    Nonotte I, Mathieu MN, Chevillard C (1989) P2-purinergic-induced ionised calcium elevation in the human promyelocytic cell line HL60. Brit J Pharmacol 96:238PGoogle Scholar
  442. 442.
    Lee H, Suh BC, Kim KT (1997) Feedback regulation of ATP-induced Ca2+ signaling in HL-60 cells is mediated by protein kinase A- and C-mediated changes in capacitative Ca2+ entry. J Biol Chem 272:21831–21838PubMedGoogle Scholar
  443. 443.
    Cowen DS, Sanders M, Dubyak G (1990) P2-purinergic receptors activate a guanine nucleotide-dependent phospholipase C in membranes from HL-60 cells. Biochim Biophys Acta 1053:195–203PubMedGoogle Scholar
  444. 444.
    Cowen DS, Baker B, Dubyak GR (1990) Pertussis toxin produces differential inhibitory effects on basal, P2-purinergic, and chemotactic peptide-stimulated inositol phospholipid breakdown in HL-60 cells and HL-60 cell membranes. J Biol Chem 265:16181–16189PubMedGoogle Scholar
  445. 445.
    Cowen DS, Berger M, Nuttle L, Dubyak GR (1991) Chronic treatment with P2-purinergic receptor agonists induces phenotypic modulation of the HL-60 and U937 human myelogenous leukemia cell lines. J Leukoc Biol 50:109–122PubMedGoogle Scholar
  446. 446.
    Ohana G, Bar-Yehuda S, Barer F, Fishman P (2001) Differential effect of adenosine on tumor and normal cell growth: focus on the A3 adenosine receptor. J Cell Physiol 186:19–23PubMedGoogle Scholar
  447. 447.
    Montero M, Garcia-Sancho J, Alvarez J (1995) Biphasic and differential modulation of Ca2+ entry by ATP and UTP in promyelocytic leukaemia HL60 cells. Biochem J 305:879–887PubMedPubMedCentralGoogle Scholar
  448. 448.
    Parker AL, Likar LL, Dawicki DD, Rounds S (1996) Mechanism of ATP-induced leukocyte adherence to cultured pulmonary artery endothelial cells. Am J Physiol 270:L695–L703PubMedGoogle Scholar
  449. 449.
    Choi SY, Kim KT (1997) Extracellular ATP-stimulated increase of cytosolic cAMP in HL-60 cells. Biochem Pharmacol 53:429–432PubMedGoogle Scholar
  450. 450.
    Jiang L, Foster FM, Ward P, Tasevski V, Luttrell BM, Conigrave AD (1997) Extracellular ATP triggers cyclic AMP-dependent differentiation of HL-60 cells. Biochem Biophys Res Commun 232:626–630PubMedGoogle Scholar
  451. 451.
    Song SK, Suh BC, Lee H, Kim KT (1997) Histamine inhibits ATP-induced [Ca2+]i rise through the activation of protein kinase A in HL-60 cells. Eur J Pharmacol 322:265–273PubMedGoogle Scholar
  452. 452.
    Conigrave AD, van der Weyden L, Holt L, Jiang L, Wilson P, Christopherson RI, Morris MB (2000) Extracellular ATP-dependent suppression of proliferation and induction of differentiation of human HL-60 leukemia cells by distinct mechanisms. Biochem Pharmacol 60:1585–1591PubMedGoogle Scholar
  453. 453.
    van der Weyden L, Rakyan V, Luttrell BM, Morris MB, Conigrave AD (2000) Extracellular ATP couples to cAMP generation and granulocytic differentiation in human NB4 promyelocytic leukaemia cells. Immunol Cell Biol 78:467–473PubMedGoogle Scholar
  454. 454.
    Adrian K, Bernhard MK, Breitinger HG, Ogilvie A (2000) Expression of purinergic receptors (ionotropic P2X1-7 and metabotropic P2Y1-11) during myeloid differentiation of HL60 cells. Biochim Biophys Acta 1492:127–138PubMedGoogle Scholar
  455. 455.
    Communi D, Janssens R, Robaye B, Zeelis N, Boeynaems JM (2000) Rapid up-regulation of P2Y messengers during granulocytic differentiation of HL-60 cells. FEBS Lett 475:39–42PubMedGoogle Scholar
  456. 456.
    Yoon MJ, Lee HJ, Kim JH, Kim DK (2006) Extracellular ATP induces apoptotic signaling in human monocyte leukemic cells, HL-60 and F-36P. Arch Pharm Res 29:1032–1041PubMedGoogle Scholar
  457. 457.
    Belton M, Commerford K, Hall J, Prato FS, Carson JJ (2008) Real-time measurement of cytosolic free calcium concentration in HL-60 cells during static magnetic field exposure and activation by ATP. Bioelectromagnetics 29:439–446PubMedGoogle Scholar
  458. 458.
    Rozanski C, Belton M, Prato FS, Carson JJ (2009) Real-time measurement of cytosolic free calcium concentration in DEM-treated HL-60 cells during static magnetic field exposure and activation by ATP. Bioelectromagnetics 30:213–221PubMedGoogle Scholar
  459. 459.
    Lee EJ, Min HY, Chung HJ, Park EJ, Shin DH, Jeong LS, Lee SK (2005) A novel adenosine analog, thio-Cl-IB-MECA, induces G0/G1 cell cycle arrest and apoptosis in human promyelocytic leukemia HL-60 cells. Biochem Pharmacol 70:918–924PubMedGoogle Scholar
  460. 460.
    Notarbartolo M, Lo CS, Meli M, Poma P, Labbozzetta M, Cervello M, D’Alessandro N (2005) Induction of apoptosis by the adenosine derivative IB-MECA in parental or multidrug-resistant HL-60 leukemia cells: possible relationship to the effects on inhibitor of apoptosis protein levels. Chemotherapy 51:272–279PubMedGoogle Scholar
  461. 461.
    Biffen M, Alexander DR (1994) Mobilization of intracellular Ca2+ by adenine nucleotides in human T-leukaemia cells: evidence for ADP-specific and P2y-purinergic receptors. Biochem J 304:769–774PubMedPubMedCentralGoogle Scholar
  462. 462.
    Chekeni FB, Elliott MR, Sandilos JK, Walk SF, Kinchen JM, Lazarowski ER, Armstrong AJ, Penuela S, Laird DW, Salvesen GS, Isakson BE, Bayliss DA, Ravichandran KS (2010) Pannexin 1 channels mediate 'find-me' signal release and membrane permeability during apoptosis. Nature 467:863–867PubMedPubMedCentralGoogle Scholar
  463. 463.
    Adinolfi E, Melchiorri L, Falzoni S, Chiozzi P, Morelli A, Tieghi A, Cuneo A, Castoldi G, Di Virgilio F, Baricordi OR (2002) P2X7 receptor expression in evolutive and indolent forms of chronic B lymphocytic leukemia. Blood 99:706–708PubMedGoogle Scholar
  464. 464.
    Cabrini G, Falzoni S, Forchap SL, Pellegatti P, Balboni A, Agostini P, Cuneo A, Castoldi G, Baricordi OR, Di Virgilio F (2005) A His-155 to Tyr polymorphism confers gain-of-function to the human P2X7 receptor of human leukemic lymphocytes. J Immunol 175:82–89PubMedGoogle Scholar
  465. 465.
    Wiley JS, Dao-Ung LP, Gu BJ, Sluyter R, Shemon AN, Li C, Taper J, Gallo J, Manoharan A (2002) A loss-of-function polymorphic mutation in the cytolytic P2X7 receptor gene and chronic lymphocytic leukaemia: a molecular study. Lancet 359:1114–1119PubMedGoogle Scholar
  466. 466.
    Dao-Ung LP, Fuller SJ, Sluyter R, SkarRatt KK, Thunberg U, Tobin G, Byth K, Ban M, Rosenquist R, Stewart GJ, Wiley JS (2004) Association of the 1513C polymorphism in the P2X7 gene with familial forms of chronic lymphocytic leukaemia. Br J Haematol 125:815–817PubMedGoogle Scholar
  467. 467.
    Zhang XJ, Zheng GG, Ma XT, Yang YH, Li G, Rao Q, Nie K, Wu KF (2004) Expression of P2X7 in human hematopoietic cell lines and leukemia patients. Leuk Res 28:1313–1322PubMedGoogle Scholar
  468. 468.
    Zhang X, Meng L, He B, Chen J, Liu P, Zhao J, Zhang Y, Li M, An D (2009) The role of P2X7 receptor in ATP-mediated human leukemia cell death: calcium influx-independent. Acta Biochim Biophys Sin (Shanghai) 41:362–369Google Scholar
  469. 469.
    Chong JH, Zheng GG, Zhu XF, Guo Y, Wang L, Ma CH, Liu SY, Xu LL, Lin YM, Wu KF (2010) Abnormal expression of P2X family receptors in Chinese pediatric acute leukemias. Biochem Biophys Res Commun 391:498–504PubMedGoogle Scholar
  470. 470.
    Cass CE, Selner M, Tan TH, Muhs WH, Robins MJ (1982) Comparison of the effects on cultured L1210 leukemia cells of the ribosyl, 2′-deoxyribosyl, and xylosyl homologs of tubercidin and adenosine alone or in combination with 2′-deoxycoformycin. Cancer Treat Rep 66:317–326PubMedGoogle Scholar
  471. 471.
    Schneider C, Wiendl H, Ogilvie A (2001) Biphasic cytotoxic mechanism of extracellular ATP on U-937 human histiocytic leukemia cells: involvement of adenosine generation. Biochim Biophys Acta 1538:190–205PubMedGoogle Scholar
  472. 472.
    Gessi S, Varani K, Merighi S, Morelli A, Ferrari D, Leung E, Baraldi PG, Spalluto G, Borea PA (2001) Pharmacological and biochemical characterization of A3 adenosine receptors in Jurkat T cells. Br J Pharmacol 134:116–126PubMedPubMedCentralGoogle Scholar
  473. 473.
    Batiuk TD, Schnizlein-Bick C, Plotkin Z, Dagher PC (2001) Guanine nucleosides and Jurkat cell death: roles of ATP depletion and accumulation of deoxyribonucleotides. Am J Physiol Cell Physiol 281:C1776–C1784PubMedGoogle Scholar
  474. 474.
    Bastin-Coyette L, Smal C, Cardoen S, Saussoy P, Van den Neste E, Bontemps F (2008) Mechanisms of cell death induced by 2-chloroadenosine in leukemic B-cells. Biochem Pharmacol 75:1451–1460PubMedGoogle Scholar
  475. 475.
    Streitová D, Weiterová L, Hofer M, Holá J, Horváth V, Kozubík A, Znojil V (2007) Effect of adenosine on the growth of human T-lymphocyte leukemia cell line MOLT-4. Cancer Invest 25:419–426PubMedGoogle Scholar
  476. 476.
    Abbracchio MP, Paoletti AM, Luini A, Cattabeni F, De Matteis MA (1992) Adenosine receptors in rat basophilic leukaemia cells: transductional mechanisms and effects on 5-hydroxytryptamine release. Br J Pharmacol 105:405–411PubMedPubMedCentralGoogle Scholar
  477. 477.
    Hilchey SP, Kobie JJ, Cochran MR, Secor-Socha S, Wang JC, Hyrien O, Burack WR, Mosmann TR, Quataert SA, Bernstein SH (2009) Human follicular lymphoma CD39+-infiltrating T cells contribute to adenosine-mediated T cell hyporesponsiveness. J Immunol 183:6157–6166PubMedPubMedCentralGoogle Scholar
  478. 478.
    Perry C, Hazan-Halevy I, Kay S, Cipok M, Grisaru D, Deutsch V, Polliack A, Naparstek E, Herishanu Y (2012) Increased CD39 expression on CD4+ T lymphocytes has clinical and prognostic significance in chronic lymphocytic leukemia. Ann Hematol 91:1271–1279PubMedGoogle Scholar
  479. 479.
    Serra S, Horenstein AL, Vaisitti T, Brusa D, Rossi D, Laurenti L, D’Arena G, Coscia M, Tripodo C, Inghirami G, Robson SC, Gaidano G, Malavasi F, Deaglio S (2011) CD73-generated extracellular adenosine in chronic lymphocytic leukemia creates local conditions counteracting drug-induced cell death. Blood 118:6141–6152PubMedPubMedCentralGoogle Scholar
  480. 480.
    Dennison JB, Balakrishnan K, Gandhi V (2009) Preclinical activity of 8-chloroadenosine with mantle cell lymphoma: roles of energy depletion and inhibition of DNA and RNA synthesis. Br J Haematol 147:297–307PubMedPubMedCentralGoogle Scholar
  481. 481.
    Robak T, Robak P (2012) Purine nucleoside analogs in the treatment of rarer chronic lymphoid leukemias. Curr Pharm Des 18:3373–3388PubMedGoogle Scholar
  482. 482.
    Fishman P, Bar-Yehuda S, Ohana G, Pathak S, Wasserman L, Barer F, Multani AS (2000) Adenosine acts as an inhibitor of lymphoma cell growth: a major role for the A3 adenosine receptor. Eur J Cancer 36:1452–1458PubMedGoogle Scholar
  483. 483.
    Chechik BE, Schrader WP, Perets A, Fernandes B (1984) Immunohistochemical localization of adenosine deaminase in human benign extrathymic lymphoid tissues and B-cell lymphomas. Cancer 53:70–78PubMedGoogle Scholar
  484. 484.
    Wiley JS, Dubyak GR (1989) Extracellular adenosine triphosphate increases cation permeability of chronic lymphocytic leukemic lymphocytes. Blood 73:1316–1323PubMedGoogle Scholar
  485. 485.
    Anghileri LJ, Plenat F, Thouvenot P (2001) Role of iron in lymphoma-induction by ATP. Oncol Rep 8:1153–1157PubMedGoogle Scholar
  486. 486.
    Kruczynski A, Mayer P, Marchand A, Vispé S, Fournier E, Annereau JP, Brel V, Barret JM, Delsol G, Imbert T, Fahy J, Bailly C (2009) Antitumor activity of pyridoisoquinoline derivatives F91873 and F91874, novel multikinase inhibitors with activity against the anaplastic lymphoma kinase. Anticancer Drugs 20:364–372PubMedGoogle Scholar
  487. 487.
    Ren S, Zhang Y, Wang Y, Lui Y, Wei W, Huang X, Mao W, Zuo Y (2010) Targeting P2X7 receptor inhibits the metastasis of murine P388D1 lymphoid neoplasm cells to lymph nodes. Cell Biol Int 34:1205–1211PubMedGoogle Scholar
  488. 488.
    Nader S, Koch-Nolte F, Haag F (2012) Activation of P2X7 causes depletion of intracellular ATP in T lymphoma cells. Purinergic Signal 8:155Google Scholar
  489. 489.
    Becher J, Nader S, Nicola J, Danquah W, Koch-Nolte F, Haag F (2012) Regulated release of ATP by Yac lymphoma cells. Immunology 137:393Google Scholar
  490. 490.
    Murgo AJ, Sistare FD (1992) K562 leukemia cells express P2T (adenosine diphosphate) purinergic receptors. J Pharmacol Exp Ther 261:580–585PubMedGoogle Scholar
  491. 491.
    Bernardo AA, Pinto-Silva FE, Persechini PM, Coutinho-Silva R, Meyer-Fernandes JR, de Souza AL, Rumjanek VM (2006) Effect of extracellular ATP on the human leukaemic cell line K562 and its multidrug counterpart. Mol Cell Biochem 289:111–124PubMedGoogle Scholar
  492. 492.
    de Rijke B, van Horssen-Zoetbrood A, Beekman JM, Otterud B, Maas F, Woestenenk R, Kester M, Leppert M, Schattenberg AV, de Witte T, van de Wiel-van KE, Dolstra H (2005) A frameshift polymorphism in P2X5 elicits an allogeneic cytotoxic T lymphocyte response associated with remission of chronic myeloid leukemia. J Clin Invest 115:3506–3516PubMedPubMedCentralGoogle Scholar
  493. 493.
    Yamaguchi M, Hirayoshi K, Okuma M, Nagata K (1994) Enhancement of differentiation induction of mouse myelomonocytic leukemic cells by extracellular ATP. J Cell Physiol 159:441–449PubMedGoogle Scholar
  494. 494.
    Wang W, Xiao J, Adachi M, Liu Z, Zhou J (2011) 4-aminopyridine induces apoptosis of human acute myeloid leukemia cells via increasing [Ca2+]i through P2X7 receptor pathway. Cell Physiol Biochem 28:199–208PubMedGoogle Scholar
  495. 495.
    Wang B, Sluyter R (2013) P2X7 receptor activation induces reactive oxygen species formation in erythroid cells. Purinergic Signal 9:101–112PubMedPubMedCentralGoogle Scholar
  496. 496.
    Gadeock S, Pupovac A, Sluyter V, Spildrejorde M, Sluyter R (2012) P2X7 receptor activation mediates organic cation uptake into human myeloid leukaemic KG-1 cells. Purinergic Signal 8:669–676PubMedPubMedCentralGoogle Scholar
  497. 497.
    Niitsu N, Honma Y (1999) Adenosine analogs as possible differentiation-inducing agents against acute myeloid leukemia. Leuk Lymphoma 34:261–271PubMedGoogle Scholar
  498. 498.
    Chakrabarti A, Gupta K, Sharma JP, Yang J, Agarwal A, Glick A, Zhang Y, Agarwal M, Agarwal MK, Wald DN (2012) ATP depletion triggers acute myeloid leukemia differentiation through an ATR/Chk1 protein-dependent and p53 protein-independent pathway. J Biol Chem 287:23635–23643PubMedPubMedCentralGoogle Scholar
  499. 499.
    Salvestrini V, Zini R, Rossi L, Gulinelli S, Manfredini R, Bianchi E, Piacibello W, Caione L, Migliardi G, Ricciardi MR, Tafuri A, Romano M, Salati S, Di Virgilio F, Ferrari S, Baccarani M, Ferrari D, Lemoli RM (2012) Purinergic signaling inhibits human acute myeloblastic leukemia cell proliferation, migration, and engraftment in immunodeficient mice. Blood 119:217–226PubMedGoogle Scholar
  500. 500.
    Racil Z, Razga F, Polakova KM, Buresova L, Polivkova V, Dvorakova D, Zackova D, Klamova H, Cetkovsky P, Mayer J (2011) Assessment of adenosine triphosphate-binding cassette subfamily B member 1 (ABCB1) mRNA expression in patients with de novo chronic myelogenous leukemia: the role of different cell types. Leuk Lymphoma 52:331–334PubMedGoogle Scholar
  501. 501.
    Constantinescu P, Wang B, Kovacevic K, Jalilian I, Bosman GJ, Wiley JS, Sluyter R (2010) P2X7 receptor activation induces cell death and microparticle release in murine erythroleukemia cells. Biochim Biophys Acta 1798:1797–1804PubMedGoogle Scholar
  502. 502.
    Schwaner I, Seifert R, Schultz G (1992) Receptor-mediated increases in cytosolic Ca2+ in the human erythroleukaemia cell line involve pertussis toxin-sensitive and -insensitive pathways. Biochem J 281:301–307PubMedPubMedCentralGoogle Scholar
  503. 503.
    Akbar GK, Dasari VR, Sheth SB, Ashby B, Mills DC, Kunapuli SP (1996) Characterization of P2 purinergic receptors on human erythro leukemia cells. J Recept Signal Transduct Res 16:209–224PubMedGoogle Scholar
  504. 504.
    Baltensperger K, Porzig H (1997) The P2U purinoceptor obligatorily engages the heterotrimeric G protein G16 to mobilize intracellular Ca2+ in human erythroleukemia cells. J Biol Chem 272:10151–10159PubMedGoogle Scholar
  505. 505.
    Spranzi E, Djeu JY, Hoffman SL, Epling-Burnette PK, Blanchard DK (1993) Lysis of human monocytic leukemia cells by extracellular adenosine triphosphate: mechanism and characterization of the adenosine triphosphate receptor. Blood 82:1578–1585PubMedGoogle Scholar
  506. 506.
    Theaker J, Fagura MS, Lawson M, Bowers KC (2000) P2X 7-induced pore formation in a population of THP-1 cells. Brit J Pharmacol 131:189PGoogle Scholar
  507. 507.
    Sherman ML, Shafman TD, Kufe DW (1988) Modulation of cyclic AMP levels and differentiation by adenosine analogs in mouse erythroleukemia cells. J Cell Physiol 134:429–436PubMedGoogle Scholar
  508. 508.
    Ryten M, Dunn PM, Neary JT, Burnstock G (2002) ATP regulates the differentiation of mammalian skeletal muscle by activation of a P2X 5 receptor on satellite cells. J Cell Biol 158:345–355PubMedPubMedCentralGoogle Scholar
  509. 509.
    Koiso K, Nemoto R, Ohtani M, Uchida K, Shimazui T, Noguchi R, Hattori K, Miyanaga N, Shiraiwa H, Iwasaki A (1991) Evaluation of the invasive potential of superficial bladder cancer by adenosine triphosphate measurement. Urol Int 46:145–148PubMedGoogle Scholar
  510. 510.
    Artim DE, Birder LA, de Groat WC (2007) Purinergic mechanisms in human bladder cancer. FASEB J 21:954.4Google Scholar
  511. 511.
    Nucciarelli F, Mearini E, Minelli A (2003) Effect of adenosine on prostate adenocarcinoma PC-3 and bladder carcinoma J82 cell lines. Drug Dev Res 58:390–395Google Scholar
  512. 512.
    Phelps PT, Anthes JC, Correll CC (2006) Characterization of adenosine receptors in the human bladder carcinoma T24 cell line. Eur J Pharmacol 536:28–37PubMedGoogle Scholar
  513. 513.
    Stella J, Bavaresco L, Braganhol E, Rockenbach L, Farias PF, Wink MR, Azambuja AA, Barrios CH, Morrone FB, Oliveira Battastini AM (2010) Differential ectonucleotidase expression in human bladder cancer cell lines. Urol Oncol 28:260–267PubMedGoogle Scholar
  514. 514.
    Blume AJ, Dalton C, Sheppard H (1973) Adenosine-mediated elevation of cyclic 3′:5′-adenosine monophosphate concentrations in cultured mouse neuroblastoma cells. Proc Natl Acad Sci U S A 70:3099–3102PubMedPubMedCentralGoogle Scholar
  515. 515.
    Blume AJ, Foster CJ (1976) Mouse neuroblastoma cell adenylate cyclase: regulation by 2-chloroadenosine, prostaglandin E1 and the cations Mg2+, Ca2+ and Mn2+. J Neurochem 26:305–311PubMedGoogle Scholar
  516. 516.
    Pénit J, Cantau B, Huot J, Jard S (1977) Adenylate cyclase from synchronized neuroblastoma cells: responsiveness to prostaglandin E1, adenosine, and dopamine during the cell cycle. Proc Natl Acad Sci U S A 74:1575–1579PubMedPubMedCentralGoogle Scholar
  517. 517.
    Green RD, Stanberry LR (1977) Elevation of cyclic AMP in C-1300 murine neuroblastoma by adenosine and related compounds and the antagonism of this response by methylxanthines. Biochem Pharmacol 26:37–43PubMedGoogle Scholar
  518. 518.
    Blume AJ (1978) Opiate binding to membrane preparations of neuroblastoma x glioma hybrid cells NG108-15: effects of ions and nucleotides. Life Sci 22:1843–1852PubMedGoogle Scholar
  519. 519.
    Hamprecht B, Brandt M, Propst F, van Calker D, Löffler F (1981) Regulation by neurohormones of cyclic AMP concentration in cells derived from the nervous system. Adv Cyclic Nucleotide Res 14:637–645PubMedGoogle Scholar
  520. 520.
    Ehrlich YH, Garfield MG, Davis TB, Kornecki E, Chaffee JE, Lenox RH (1986) Extracellular protein phosphorylation systems in the regulation of neuronal function. Prog Brain Res 69:197–208PubMedGoogle Scholar
  521. 521.
    Chau LY, Lin TA, Chang WT, Chen CH, Shue MJ, Hsu YS, Hu CY, Tsai WH, Sun GY (1993) Endothelin-mediated calcium response and inositol 1,4,5-trisphosphate release in neuroblastoma-glioma hybrid cells (NG108-15): cross talk with ATP and bradykinin. J Neurochem 60:454–460PubMedGoogle Scholar
  522. 522.
    Chueh SH, Kao LS (1993) Extracellular ATP stimulates calcium influx in neuroblastoma x glioma hybrid NG108-15 cells. J Neurochem 61:1782–1788PubMedGoogle Scholar
  523. 523.
    Okajima F, Tomura H, Kondo Y (1993) Enkephalin activates the phospholipase C/Ca2+ system through cross-talk between opioid receptors and P2-purinergic or bradykinin receptors in NG 108–15 cells. A permissive role for pertussis toxin-sensitive G-proteins. Biochem J 290:241–247PubMedPubMedCentralGoogle Scholar
  524. 524.
    Reetz G, Reiser G (1994) Cross-talk of the receptors for bradykinin, serotonin, and ATP shown by single cell Ca2+ responses indicating different modes of Ca2+ activation in a neuroblastoma x glioma hybrid cell line. J Neurochem 62:890–897PubMedGoogle Scholar
  525. 525.
    Filippov AK, Brown DA (1996) Activation of nucleotide receptors inhibits high-threshold calcium currents in NG108-15 neuronal hybrid cells. Eur J Neurosci 8:1149–1155PubMedGoogle Scholar
  526. 526.
    Sak K, Kelve M, Uri A, Järv J (1998) Pyrimidinoceptor potentiation by ATP in NG108-15 cells. FEBS Lett 439:107–109PubMedGoogle Scholar
  527. 527.
    Lin TA, Lustig KD, Sportiello MG, Weisman GA, Sun GY (1993) Signal transduction pathways coupled to a P2U receptor in neuroblastoma x glioma (NG108-15) cells. J Neurochem 60:1115–1125PubMedGoogle Scholar
  528. 528.
    Filippov AK, Selyanko AA, Robbins J, Brown DA (1994) Activation of nucleotide receptors inhibits M-type K current [I K(M)] in neuroblastoma x glioma hybrid cells. Pflugers Arch 429:223–230PubMedGoogle Scholar
  529. 529.
    Reiser G (1995) Ca2+- and nitric oxide-dependent stimulation of cyclic GMP synthesis in neuronal cell line induced by P2-purinergic/pyrimidinergic receptor. J Neurochem 64:61–68PubMedGoogle Scholar
  530. 530.
    Song SL, Chueh SH (1996) Antagonistic effect of Na + and Mg2+ on P2z purinoceptor-associated pores in dibutyryl cyclic AMP-differentiated NG108-15 cells. J Neurochem 67:1694–1701PubMedGoogle Scholar
  531. 531.
    Kaiho H, Kimura J, Matsuoka I, Kumasaka T, Nakanishi H (1996) ATP-activated nonselective cation current in NG108-15 cells. J Neurochem 67:398–406PubMedGoogle Scholar
  532. 532.
    Kaiho H, Matsuoka I, Kimura J, Nakanishi H (1998) Identification of P2X7 (P2Z) receptor in N18TG-2 cells and NG108-15 cells. J Neurochem 70:951–957PubMedGoogle Scholar
  533. 533.
    Bräter M, Li SN, Gorodezkaya IJ, Andreas K, Ravens U (1999) Voltage-sensitive Ca2+ channels, intracellular Ca2+ stores and Ca2+-release-activated Ca2+ channels contribute to the ATP-induced [Ca2+]i increase in differentiated neuroblastoma x glioma NG 108–15 cells. Neurosci Lett 264:97–100PubMedGoogle Scholar
  534. 534.
    Watano T, Matsuoka I, Kimura J (2002) Characteristics of ATP-induced current through P2X7 receptor in NG108-15 cells: unique antagonist sensitivity and lack of pore formation. Jpn J Pharmacol 88:428–435PubMedGoogle Scholar
  535. 535.
    Sak K, Webb TE, Samuel K, Kelve M, Järv J (1999) Only pyrimidinoceptors are functionally expressed in mouse neuroblastoma cell lines. Mol Cell Biol Res Commun 1:203–208PubMedGoogle Scholar
  536. 536.
    Sak K, Samuel K, Kelve M, Webb TE (2001) Pharmacological characterisation of pyrimidinoceptor responses in NG108-15 cells. Eur J Pharmacol 415:127–133PubMedGoogle Scholar
  537. 537.
    Apolloni S, Finocchi P, D’Agnano I, Alloisio S, Nobile M, D’Ambrosi N, Volonté C (2010) UDP exerts cytostatic and cytotoxic actions in human neuroblastoma SH-SY5Y cells over-expressing P2Y6 receptor. Neurochem Int 56:670–678PubMedGoogle Scholar
  538. 538.
    Ohkubo S, Kimura J, Matsuoka I (2000) Ecto-alkaline phosphatase in NG108-15 cells: a key enzyme mediating P1 antagonist-sensitive ATP response. Br J Pharmacol 131:1667–1672PubMedPubMedCentralGoogle Scholar
  539. 539.
    Kaulich M, Qurishi R, Müller CE (2003) Extracellular metabolism of nucleotides in neuroblastoma x glioma NG108-15 cells determined by capillary electrophoresis. Cell Mol Neurobiol 23:349–364PubMedGoogle Scholar
  540. 540.
    Van Zoelen EJ, Tertoolen LG, Boonstra J, Van der Saag PT, De Laat SW (1982) Effect of external ATP on the plasma membrane permeability and (Na+ + K+)-ATPase activity of mouse neuroblastoma cells. Biochim Biophys Acta 720:223–234PubMedGoogle Scholar
  541. 541.
    Chen CC, Chen WC (1997) P2Y receptor linked to phospholipase C: stimulation of neuro 2A cells by UTP and ATP and possible regulation by protein kinase C subtype ε. J Neurochem 69:1409–1416PubMedGoogle Scholar
  542. 542.
    Iredale PA, Martin KF, Alexander SP, Hill SJ, Kendall DA (1992) Inositol 1,4,5-trisphosphate generation and calcium mobilisation via activation of an atypical P2 receptor in the neuronal cell line, N1E-115. Br J Pharmacol 107:1083–1087PubMedPubMedCentralGoogle Scholar
  543. 543.
    Schrier SM, Florea BI, Mulder GJ, Nagelkerke JF, Ijzerman AP (2002) Apoptosis induced by extracellular ATP in the mouse neuroblastoma cell line N1E-115: studies on involvement of P2 receptors and adenosine. Biochem Pharmacol 63:1119–1126PubMedGoogle Scholar
  544. 544.
    Watano T, Matsuoka I, Ogawa K, Kimura J (2002) Effects of anions on ATP-induced [Ca2+]i increase in NG108-15 cells. Jpn J Pharmacol 89:302–308PubMedGoogle Scholar
  545. 545.
    Garritsen A, Zhang Y, Cooper DM (1992) Purinergic receptor regulation of signal transduction in NCB-20 cells. Mol Pharmacol 41:743–749PubMedGoogle Scholar
  546. 546.
    Delporte C, Winand J, Poloczek P, Brunko E, Tastenoy M, Waelbroeck M, Christophe J (1992) Inhibitory effects of ATP and other nucleotides on atrial natriuretic peptide (ANP) binding to R1-type ANP receptors in human neuroblastoma NB-OK-1 cell membranes. Biochim Biophys Acta 1135:323–329PubMedGoogle Scholar
  547. 547.
    Soares Lemos V, Bucher B, Takeda K (1997) Neuropeptide Y modulates ATP-induced increases in internal calcium via the adenylate cyclase/protein kinase A system in a human neuroblastoma cell line. Biochem J 321:439–444PubMedPubMedCentralGoogle Scholar
  548. 548.
    El-Sherif Y, Wieraszko A, Banerjee P, Penington NJ (2001) ATP modulates Na+ channel gating and induces a non-selective cation current in a neuronal hippocampal cell line. Brain Res 904:307–317PubMedGoogle Scholar
  549. 549.
    Larsson KP, Hansen AJ, Dissing S (2002) The human SH-SY5Y neuroblastoma cell-line expresses a functional P2X7 purinoceptor that modulates voltage-dependent Ca2+ channel function. J Neurochem 83:285–298PubMedGoogle Scholar
  550. 550.
    Guarnieri S, Pilla R, Morabito C, Sacchetti S, Mancinelli R, Fanò G, Mariggiò MA (2009) Extracellular guanosine and GTP promote expression of differentiation markers and induce S-phase cell-cycle arrest in human SH-SY5Y neuroblastoma cells. Int J Dev Neurosci 27:135–147PubMedGoogle Scholar
  551. 551.
    Canals M, Angulo E, Casadó V, Canela EI, Mallol J, Viñals F, Staines W, Tinner B, Hillion J, Agnati L, Fuxe K, Ferré S, Lluis C, Franco R (2005) Molecular mechanisms involved in the adenosine A1 and A2A receptor-induced neuronal differentiation in neuroblastoma cells and striatal primary cultures. J Neurochem 92:337–348PubMedGoogle Scholar
  552. 552.
    Lee H, Choi BH, Suh BC, Lee SK, Kim KT (2003) Attenuation of signal flow from P2Y6 receptor by protein kinase C-alpha in SK-N-BE(2)C human neuroblastoma cells. J Neurochem 85:1043–1053PubMedGoogle Scholar
  553. 553.
    Gualix J, León-Otegui M, Recuero M, Bullido MJ, Valdivieso F, Miras-Portugal MT (2008) Presence of functional P2Y1 and P2Y1 receptors in human SK-N-MC neuroblastoma cells. Purinergic Signal 4:S210Google Scholar
  554. 554.
    Chelmicka-Schorr E, Jones KH, Checinski ME, Yu RC, Arnason BG (1985) Influence of the sympathetic nervous system on the growth of neuroblastoma in vivo and in vitro. Cancer Res 45:6213–6215PubMedGoogle Scholar
  555. 555.
    Burnstock G, Verkhratsky A (2010) Long-term (trophic) purinergic signalling: purinoceptors control cell proliferation, differentiation and death. Cell Death and Disease 1:e9PubMedPubMedCentralGoogle Scholar
  556. 556.
    Silei V, Politi V, Lauro GM (2000) Uridine induces differentiation in human neuroblastoma cells via protein kinase C epsilon. J Neurosci Res 61:206–211PubMedGoogle Scholar
  557. 557.
    Cavaliere F, Nestola V, Amadio S, D’Ambrosi N, Angelini DF, Sancesario G, Bernardi G, Volonté C (2005) The metabotropic P2Y4 receptor participates in the commitment to differentiation and cell death of human neuroblastoma SH-SY5Y cells. Neurobiol Dis 18:100–109PubMedGoogle Scholar
  558. 558.
    Han JZ, Lin W, Chen YZ (2005) Inhibition of ATP-induced calcium influx in HT4 cells by glucocorticoids: involvement of protein kinase A. Acta Pharmacol Sin 26:199–204PubMedGoogle Scholar
  559. 559.
    Raffaghello L, Chiozzi P, Falzoni S, Di VF, Pistoia V (2006) The P2X7 receptor sustains the growth of human neuroblastoma cells through a substance P-dependent mechanism. Cancer Res 66:907–914PubMedGoogle Scholar
  560. 560.
    Schrier SM, van Tilburg EW, van der Meulen H, Ijzerman AP, Mulder GJ, Nagelkerke JF (2001) Extracellular adenosine-induced apoptosis in mouse neuroblastoma cells: studies on involvement of adenosine receptors and adenosine uptake. Biochem Pharmacol 61:417–425PubMedGoogle Scholar
  561. 561.
    Lakshmi S, Joshi PG (2006) Activation of Src/kinase/phospholipase C/mitogen-activated protein kinase and induction of neurite expression by ATP, independent of nerve growth factor. Neuroscience 141:179–189PubMedGoogle Scholar
  562. 562.
    Wu PY, Lin YC, Chang CL, Lu HT, Chin CH, Hsu TT, Chu D, Sun SH (2009) Functional decreases in P2X7 receptors are associated with retinoic acid-induced neuronal differentiation of Neuro-2a neuroblastoma cells. Cell Signal 21:881–891PubMedGoogle Scholar
  563. 563.
    Morgan CR, Bird EV, Robinson PP, Boissonade FM (2009) Immunohistochemical analysis of the purinoceptor P2X7 in human lingual nerve neuromas. J Orofac Pain 23:65–72PubMedGoogle Scholar
  564. 564.
    Gutiérrez-Martín Y, Bustillo D, Gómez-Villafuertes R, Sánchez-Nogueiro J, Torregrosa-Hetland C, Binz T, Gutiérrez LM, Miras-Portugal MT, Artalejo AR (2011) P2X7 receptors trigger ATP exocytosis and modify secretory vesicle dynamics in neuroblastoma cells. J Biol Chem 286:11370–11381PubMedPubMedCentralGoogle Scholar
  565. 565.
    Sun SH (2010) Roles of P2X7 receptor in glial and neuroblastoma cells: the therapeutic potential of P2X7 receptor antagonists. Mol Neurobiol 41:351–355PubMedGoogle Scholar
  566. 566.
    Snell CR, Snell PH (1984) Benzodiazepines modulate the A2 adenosine binding sites on 108CC15 neuroblastoma X glioma hybrid cells. Br J Pharmacol 83:791–798PubMedPubMedCentralGoogle Scholar
  567. 567.
    Abbracchio MP, Cattabeni F, Clementi F, Sher E (1989) Adenosine receptors linked to adenylate cyclase activity in human neuroblastoma cells: modulation during cell differentiation. Neuroscience 30:819–825PubMedGoogle Scholar
  568. 568.
    Dehnhardt M, Palm C, Vieten A, Bauer A, Pietrzyk U (2007) Quantifying the A1AR distribution in peritumoural zones around experimental F98 and C6 rat brain tumours. J Neurooncol 85:49–63PubMedGoogle Scholar
  569. 569.
    Lantos PL (1974) The fine structural localisation of thiamine pyrophosphatase and adenosine triphosphatase in neural tumours induced by N-ethyl-N-nitrosourea in rats. Acta Neuropathol 29:199–209PubMedGoogle Scholar
  570. 570.
    Grobben B, Anciaux K, Roymans D, Stefan C, Bollen M, Esmans EL, Slegers H (1999) An ecto-nucleotide pyrophosphatase is one of the main enzymes involved in the extracellular metabolism of ATP in rat C6 glioma. J Neurochem 72:826–834PubMedGoogle Scholar
  571. 571.
    Grobben B, Claes P, Roymans D, Esmans EL, Van Onckelen H, Slegers H (2000) Ecto-nucleotide pyrophosphatase modulates the purinoceptor-mediated signal transduction and is inhibited by purinoceptor antagonists. Br J Pharmacol 130:139–145PubMedPubMedCentralGoogle Scholar
  572. 572.
    Wink MR, Lenz G, Braganhol E, Tamajusuku AS, Schwartsmann G, Sarkis JJ, Battastini AM (2003) Altered extracellular ATP, ADP and AMP catabolism in glioma cell lines. Cancer Lett 198:211–218PubMedGoogle Scholar
  573. 573.
    Wink MR, Tamajusuku AS, Braganhol E, Casali EA, Barreto-Chaves ML, Sarkis JJ, Battastini AM (2003) Thyroid hormone upregulates ecto-5′-nucleotidase/CD73 in C6 rat glioma cells. Mol Cell Endocrinol 205:107–114PubMedGoogle Scholar
  574. 574.
    Braganhol E, Tamajusuku AS, Bernardi A, Wink MR, Battastini AM (2007) Ecto-5′-nucleotidase/CD73 inhibition by quercetin in the human U138MG glioma cell line. Biochim Biophys Acta 1770:1352–1359PubMedGoogle Scholar
  575. 575.
    Cappellari AR, Vasques GJ, Bavaresco L, Braganhol E, Battastini AM (2012) Involvement of ecto-5′-nucleotidase/CD73 in U138MG glioma cell adhesion. Mol Cell Biochem 359:315–322PubMedGoogle Scholar
  576. 576.
    Cappellari AR, Rockenbach L, Dietrich F, Clarimundo V, Glaser T, Braganhol E, Abujamra AL, Roesler R, Ulrich H, Battastini AM (2012) Characterization of ectonucleotidases in human medulloblastoma cell lines: ecto-5′NT/CD73 in metastasis as potential prognostic factor. PLoS One 7:e47468PubMedPubMedCentralGoogle Scholar
  577. 577.
    Braganhol E, Morrone FB, Bernardi A, Huppes D, Meurer L, Edelweiss MI, Lenz G, Wink MR, Robson SC, Battastini AM (2009) Selective NTPDase2 expression modulates in vivo rat glioma growth. Cancer Sci 100:1434–1442PubMedGoogle Scholar
  578. 578.
    Braganhol E, Zanin RF, Bernardi A, Bergamin LS, Cappellari AR, Campesato LF, Morrone FB, Campos MM, Calixto JB, Edelweiss MI, Wink MR, Sévigny J, Robson SC, Battastini AM (2012) Overexpression of NTPDase2 in gliomas promotes systemic inflammation and pulmonary injury. Purinergic Signal 8:235–243PubMedPubMedCentralGoogle Scholar
  579. 579.
    Baba T, Fukui M, Sakata S, Tashima T, Takeshita I, Nakamura T, Inoue T (1989) Selective enhancement of intratumoural blood flow in malignant gliomas: experimental study in rats by intracarotid administration of adenosine or adenosine triphosphate. Acta Neurochir (Wien) 101:66–74Google Scholar
  580. 580.
    Natori Y, Baba T, Moriguchi M, Takeshita I, Fukui M (1992) Effects of theophylline on the selective increases in intratumoral blood flow induced by intracarotid infusion of adenosine and adenosine triphosphate in C6 glioma-transplanted rat brains. Surg Neurol 37:8–14PubMedGoogle Scholar
  581. 581.
    Kitanaka J, Hashimoto H, Gotoh M, Mayumi T, Baba A (1992) Mechanism of extracellular ATP-stimulated phosphoinositide hydrolysis in rat glioma C6 cells. J Pharmacol Exp Ther 263:1248–1252PubMedGoogle Scholar
  582. 582.
    Sabala P, Amler E, Baranska J (1997) Intracellular Ca2+ signals induced by ATP and thapsigargin in glioma C6 cells. Calcium pools sensitive to inositol 1,4,5-trisphosphate and thapsigargin. Neurochem Int 31:55–64PubMedGoogle Scholar
  583. 583.
    Valeins H, Merle M, Labouesse J (1992) Pre-steady state study of β-adrenergic and purinergic receptor interaction in C6 cell membranes: undelayed balance between positive and negative coupling to adenylyl cyclase. Mol Pharmacol 42:1033–1041PubMedGoogle Scholar
  584. 584.
    Munshi R, DeBernardi MA, Brooker G (1993) P2U-purinergic receptors on C6-2B rat glioma cells: modulation of cytosolic Ca2+ and cAMP levels by protein kinase C. Mol Pharmacol 44:1185–1191PubMedGoogle Scholar
  585. 585.
    Lazarowski ER, Harden TK (1994) Identification of a uridine nucleotide-selective G-protein-linked receptor that activates phospholipase C. J Biol Chem 269:11830–11836PubMedGoogle Scholar
  586. 586.
    Boyer JL, Zohn IE, Jacobson KA, Harden TK (1994) Differential effects of P2-purinoceptor antagonists on phospholipase C- and adenylyl cyclase-coupled P2Y-purinoceptors. Br J Pharmacol 113:614–620PubMedPubMedCentralGoogle Scholar
  587. 587.
    Lin WW, Chuang DM (1994) Different signal transduction pathways are coupled to the nucleotide receptor and the P2Y receptor in C6 glioma cells. J Pharmacol Exp Ther 269:926–931PubMedGoogle Scholar
  588. 588.
    Sabala P, Czajkowski R, Przybylek K, Kalita K, Kaczmarek L, Baranska J (2001) Two subtypes of G protein-coupled nucleotide receptors, P2Y1 and P2Y2 are involved in calcium signalling in glioma C6 cells. Br J Pharmacol 132:393–402PubMedPubMedCentralGoogle Scholar
  589. 589.
    Czajkowski R, Lei L, Sabala P, Baranska J (2002) ADP-evoked phospholipase C stimulation and adenylyl cyclase inhibition in glioma C6 cells occur through two distinct nucleotide receptors, P2Y1 and P2Y12. FEBS Lett 513:179–183PubMedGoogle Scholar
  590. 590.
    Baranska J, Czajkowski R, Sabala P (2004) Cross-talks between nucleotide receptor-induced signaling pathways in serum-deprived and non-starved glioma C6 cells. Adv Enzyme Regul 44:219–232PubMedGoogle Scholar
  591. 591.
    Suplat D, Krzeminski P, Pomorski P, Baranska J (2007) P2Y1 and P2Y12 receptor cross-talk in calcium signalling: evidence from nonstarved and long-term serum-deprived glioma C6 cells. Purinergic Signal 3:221–230PubMedPubMedCentralGoogle Scholar
  592. 592.
    Krzeminski P, Suplat D, Czajkowski R, Pomorski P, Baranska J (2007) Expression and functional characterization of P2Y1 and P2Y12 nucleotide receptors in long-term serum-deprived glioma C6 cells. FEBS J 274:1970–1982PubMedGoogle Scholar
  593. 593.
    López-Valdés HE, Beltran-Parrazal L, Brennan KC, Charles AC (2010) Bradykinin increases resensitization of purinergic receptor signaling in glioma cells. Cancer Cell Int 10:35PubMedPubMedCentralGoogle Scholar
  594. 594.
    Wypych D, Pomorski P (2012) P2Y1 nucleotide receptor silencing and its effect on glioma C6 calcium signaling. Acta Biochim Pol 59:711–717PubMedGoogle Scholar
  595. 595.
    Krzeminski P, Pomorski P, Baranska J (2008) The P2Y14 receptor activity in glioma C6 cells. Eur J Pharmacol 594:49–54PubMedGoogle Scholar
  596. 596.
    Wei W, Ryu JK, Choi HB, McLarnon JG (2008) Expression and function of the P2X7 receptor in rat C6 glioma cells. Cancer Lett 260:79–87PubMedGoogle Scholar
  597. 597.
    Tamajusuku AS, Villodre ES, Paulus R, Coutinho-Silva R, Battasstini AM, Wink MR, Lenz G (2010) Characterization of ATP-induced cell death in the GL261 mouse glioma. J Cell Biochem 109:983–991PubMedGoogle Scholar
  598. 598.
    Gehring MP, Pereira TC, Zanin RF, Borges MC, Braga FA, Battastini AM, Bogo MR, Lenz G, Campos MM, Morrone FB (2012) P2X7 receptor activation leads to increased cell death in a radiosensitive human glioma cell line. Purinergic Signal 8:729–739PubMedPubMedCentralGoogle Scholar
  599. 599.
    Fang KM, Wang YL, Huang MC, Sun SH, Cheng H, Tzeng SF (2011) Expression of macrophage inflammatory protein-1α and monocyte chemoattractant protein-1 in glioma-infiltrating microglia: involvement of ATP and P2X7 receptor. J Neurosci Res 89:199–211PubMedGoogle Scholar
  600. 600.
    Guo LH, Trautmann K, Schluesener HJ (2004) Expression of P2X4 receptor in rat C6 glioma by tumor-associated macrophages and activated microglia. J Neuroimmunol 152:67–72PubMedGoogle Scholar
  601. 601.
    Ågren G, Ronquist G (1975) On the availability of certain metabolites at the outer surface of normal and malignant cells for the membranous de novo synthesis of ATP and other nucleotides. Ups J Med Sci 80:1–4PubMedGoogle Scholar
  602. 602.
    Ravera S, Aluigi MG, Calzia D, Ramoino P, Morelli A, Panfoli I (2011) Evidence for ectopic aerobic ATP production on C6 glioma cell plasma membrane. Cell Mol Neurobiol 31:313–321PubMedGoogle Scholar
  603. 603.
    Sinclair CJ, LaRivière CG, Young JD, Cass CE, Baldwin SA, Parkinson FE (2000) Purine uptake and release in rat C6 glioma cells: nucleoside transport and purine metabolism under ATP-depleting conditions. J Neurochem 75:1528–1538PubMedGoogle Scholar
  604. 604.
    Tressler AM, Lai C, Naus C, Dubyak G (2011) Gating of pannexin 1-mediated ATP release channels by mechanical stress stimuli. FASEB J 25:1007.3Google Scholar
  605. 605.
    Jantaratnotai N, Choi HB, McLarnon JG (2009) ATP stimulates chemokine production via a store-operated calcium entry pathway in C6 glioma cells. BMC Cancer 9:442PubMedPubMedCentralGoogle Scholar
  606. 606.
    Zhang W, Turner DJ, Segura BJ, Cowles R, Mulholland MW (2000) ATP induces c-fos expression in C6 glioma cells by activation of P2Y receptors. J Surg Res 94:49–55PubMedGoogle Scholar
  607. 607.
    Jantaratnotai N, McLarnon JG (2011) Calcium dependence of purinergic subtype P2Y receptor modulation of C6 glioma cell migration. Neurosci Lett 497:80–84PubMedGoogle Scholar
  608. 608.
    Tu MT, Luo SF, Wang CC, Chien CS, Chiu CT, Lin CC, Yang CM (2000) P2Y2 receptor-mediated proliferation of C6 glioma cells via activation of Ras/Raf/MEK/MAPK pathway. Br J Pharmacol 129:1481–1489PubMedPubMedCentralGoogle Scholar
  609. 609.
    Claes P, Grobben B, Van Kolen K, Roymans D, Slegers H (2001) P2YAC-receptor agonists enhance the proliferation of rat C6 glioma cells through activation of the p42/44 mitogen-activated protein kinase. Br J Pharmacol 134:402–408PubMedPubMedCentralGoogle Scholar
  610. 610.
    Morrone FB, Jacques-Silva MC, Horn AP, Bernardi A, Schwartsmann G, Rodnight R, Lenz G (2003) Extracellular nucleotides and nucleosides induce proliferation and increase nucleoside transport in human glioma cell lines. J Neurooncol 64:211–218PubMedGoogle Scholar
  611. 611.
    Claes P, Van Kolen K, Roymans D, Blero D, Vissenberg K, Erneux C, Verbelen JP, Esmans EL, Slegers H (2004) Reactive blue 2 inhibition of cyclic AMP-dependent differentiation of rat C6 glioma cells by purinergic receptor-independent inactivation of phosphatidylinositol 3-kinase. Biochem Pharmacol 67:1489–1498PubMedGoogle Scholar
  612. 612.
    Czajkowski R, Banachewicz W, Ilnytska O, Drobot LB, Baranska J (2004) Differential effects of P2Y1 and P2Y12 nucleotide receptors on ERK1/ERK2 and phosphatidylinositol 3-kinase signalling and cell proliferation in serum-deprived and nonstarved glioma C6 cells. Br J Pharmacol 141:497–507PubMedPubMedCentralGoogle Scholar
  613. 613.
    Van Kolen K, Gilany K, Moens L, Esmans EL, Slegers H (2006) P2Y12 receptor signalling towards PKB proceeds through IGF-I receptor cross-talk and requires activation of Src, Pyk2 and Rap1. Cell Signal 18:1169–1181PubMedGoogle Scholar
  614. 614.
    Claes P, Slegers H (2004) P2Y receptor activation affects the proliferation and differentiation of glial and neuronal cells: a focus on rat C6 glioma cells. Curr Neuropharmacol 2:207–220Google Scholar
  615. 615.
    Langeveld CH, Jongenelen CA, Heimans JJ, Stoof JC (1992) Growth inhibition of human glioma cells induced by 8-chloroadenosine, an active metabolite of 8-chloro cyclic adenosine 3′:5′-monophosphate. Cancer Res 52:3994–3999PubMedGoogle Scholar
  616. 616.
    Zorn M, Maronde E, Jastorff B, Richter-Landsberg C (1993) Differential effects of two structurally related N6-substituted cAMP analogues on C6 glioma cells. Eur J Cell Biol 60:351–357PubMedGoogle Scholar
  617. 617.
    Castillo CA, Albasanz JL, Fernández M, Martín M (2007) Endogenous expression of adenosine A1, A2 and A3 receptors in rat C6 glioma cells. Neurochem Res 32:1056–1070PubMedGoogle Scholar
  618. 618.
    Ohkubo S, Nagata K, Nakahata N (2007) Adenosine uptake-dependent C6 cell growth inhibition. Eur J Pharmacol 577:35–43PubMedGoogle Scholar
  619. 619.
    Castillo CA, León D, Ruiz MA, Albasanz JL, Martín M (2008) Modulation of adenosine A1 and A2A receptors in C6 glioma cells during hypoxia: involvement of endogenous adenosine. J Neurochem 105:2315–2329PubMedGoogle Scholar
  620. 620.
    Morrone FB, Horn AP, Stella J, Spiller F, Sarkis JJ, Salbego CG, Lenz G, Battastini AM (2005) Increased resistance of glioma cell lines to extracellular ATP cytotoxicity. J Neurooncol 71:135–140PubMedGoogle Scholar
  621. 621.
    Morrone FB, Oliveira DL, Gamermann P, Stella J, Wofchuk S, Wink MR, Meurer L, Edelweiss MI, Lenz G, Battastini AM (2006) In vivo glioblastoma growth is reduced by apyrase activity in a rat glioma model. BMC Cancer 6:226PubMedPubMedCentralGoogle Scholar
  622. 622.
    Katayama M, Kawaguchi T, Berger MS, Pieper RO (2007) DNA damaging agent-induced autophagy produces a cytoprotective adenosine triphosphate surge in malignant glioma cells. Cell Death Differ 14:548–558PubMedGoogle Scholar
  623. 623.
    Renner C, Asperger A, Seyffarth A, Meixensberger J, Gebhardt R, Gaunitz F (2010) Carnosine inhibits ATP production in cells from malignant glioma. Neurol Res 32:101–105PubMedGoogle Scholar
  624. 624.
    Hartmann J, Verkhratsky A (1998) Relations between intracellular Ca2+ stores and store-operated Ca 2+ entry in primary cultured human glioblastoma cells. J Physiol 513:411–424PubMedPubMedCentralGoogle Scholar
  625. 625.
    de Joannon AC, Mancini F, Landolfi C, Soldo L, Leta A, Ruggieri A, Mangano G, Polenzani L, Pinza M, Milanese C (2000) Adenosine triphosphate affects interleukin −1β release by T98G glioblastoma cells through a purinoceptor-independent mechanism. Neurosci Lett 285:218–222PubMedGoogle Scholar
  626. 626.
    Ledur PF, Villodre ES, Paulus R, Cruz LA, Flores DG, Lenz G (2012) Extracellular ATP reduces tumor sphere growth and cancer stem cell population in glioblastoma cells. Purinergic Signal 8:39–48PubMedPubMedCentralGoogle Scholar
  627. 627.
    Zeng D, Maa T, Wang U, Feoktistov I, Biaggioni I, Belardinelli L (2004) Expression and function of A2B adenosine receptors in the U87MG tumor cells. Drug Dev Res 58:405–411Google Scholar
  628. 628.
    Synowitz M, Glass R, Färber K, Markovic D, Kronenberg G, Herrmann K, Schnermann J, Nolte C, van Rooijen N, Kiwit J, Kettenmann H (2006) A1 adenosine receptors in microglia control glioblastoma-host interaction. Cancer Res 66:8550–8557PubMedGoogle Scholar
  629. 629.
    Merighi S, Benini A, Mirandola P, Gessi S, Varani K, Leung E, Maclennan S, Borea PA (2006) Adenosine modulates vascular endothelial growth factor expression via hypoxia-inducible factor-1 in human glioblastoma cells. Biochem Pharmacol 72:19–31PubMedGoogle Scholar
  630. 630.
    Gessi S, Sacchetto V, Fogli E, Merighi S, Varani K, Baraldi PG, Tabrizi MA, Leung E, Maclennan S, Borea PA (2010) Modulation of metalloproteinase-9 in U87MG glioblastoma cells by A3 adenosine receptors. Biochem Pharmacol 79:1483–1495PubMedGoogle Scholar
  631. 631.
    Vincenzi F, Targa M, Corciulo C, Gessi S, Merighi S, Setti S, Cadossi R, Borea PA, Varani K (2012) The anti-tumor effect of A3 adenosine receptors is potentiated by pulsed electromagnetic fields in cultured neural cancer cells. PLoS One 7:e39317PubMedPubMedCentralGoogle Scholar
  632. 632.
    Kim TH, Kim YK, Woo JS (2012) The adenosine A3 receptor agonist Cl-IB-MECA induces cell death through Ca2+/ROS-dependent down regulation of ERK and Akt in A172 human glioma cells. Neurochem Res 37:2667–2677PubMedGoogle Scholar
  633. 633.
    Clark RB, Gross R, Su YF, Perkins JP (1974) Regulation of adenosine 3′:5′-monophosphate content in human astrocytoma cells by adenosine and the adenine nucleotides. J Biol Chem 249:5296–5303PubMedGoogle Scholar
  634. 634.
    Hughes AR, Harden TK (1986) Adenosine and muscarinic cholinergic receptors attenuate cyclic AMP accumulation by different mechanisms in 1321N1 astrocytoma cells. J Pharmacol Exp Ther 237:173–178PubMedGoogle Scholar
  635. 635.
    Rathbone MP, Middlemiss PJ, Kim JK, Gysbers JW, DeForge SP, Smith RW, Hughes DW (1992) Adenosine and its nucleotides stimulate proliferation of chick astrocytes and human astrocytoma cells. Neurosci Res 13:1–17PubMedGoogle Scholar
  636. 636.
    Bradley KK, Bradley ME (2001) Purine nucleoside-dependent inhibition of cellular proliferation in 1321N1 human astrocytoma cells. J Pharmacol Exp Ther 299:748–752PubMedGoogle Scholar
  637. 637.
    Sellers LA, Simon J, Lundahl TS, Cousens DJ, Humphrey PP, Barnard EA (2001) Adenosine nucleotides acting at the human P2Y1 receptor stimulate mitogen-activated protein kinases and induce apoptosis. J Biol Chem 276:16379–16390PubMedGoogle Scholar
  638. 638.
    Gendron FP, Neary JT, Theiss PM, Sun GY, Gonzalez FA, Weisman GA (2003) Mechanisms of P2X7 receptor-mediated ERK1/2 phosphorylation in human astrocytoma cells. Am J Physiol Cell Physiol 284:C571–C581PubMedGoogle Scholar
  639. 639.
    Kim SG, Gao ZG, Soltysiak KA, Chang TS, Brodie C, Jacobson KA (2003) P2Y6 nucleotide receptor activates PKC to protect 1321N1 astrocytoma cells against tumor necrosis factor-induced apoptosis. Cell Mol Neurobiol 23:401–418PubMedPubMedCentralGoogle Scholar
  640. 640.
    Ho MKC, Simon J, Barnard EA, Wong YH (2004) Atypical regulation of calcium signals in astrocytoma 1321N1 cells expressing the purinergic P2Y12 receptor. J Neurochem 88:P33–15Google Scholar
  641. 641.
    Flores RV, Casallas-Bond A, Garrad R, Weisman GA, Gonzalez FA (2004) Signaling of a P2y2 receptor—EGFP fusion protein expressed in 1321N1 astrocytoma cells. Society for Neuroscience Abstract Viewer/Itinerary Planner, Washington, Program No.631.6Google Scholar
  642. 642.
    Kreda SM, Seminario-Vidal L, Heusden C, Lazarowski ER (2008) Thrombin-promoted release of UDP-glucose from human astrocytoma cells. Br J Pharmacol 153:1528–1537PubMedPubMedCentralGoogle Scholar
  643. 643.
    Blum AE, Walsh BC, Dubyak GR (2010) Extracellular osmolarity modulates G protein-coupled receptor-dependent ATP release from 1321N1 astrocytoma cells. Am J Physiol Cell Physiol 298:C386–C396PubMedPubMedCentralGoogle Scholar
  644. 644.
    Fiebich BL, Biber K, Gyufko K, Berger M, Bauer J, van Calker D (1996) Adenosine A2b receptors mediate an increase in interleukin (IL)-6 mRNA and IL-6 protein synthesis in human astroglioma cells. J Neurochem 66:1426–1431PubMedGoogle Scholar
  645. 645.
    Abbracchio MP, Rainaldi G, Giammarioli AM, Ceruti S, Brambilla R, Cattabeni F, Barbieri D, Franceschi C, Jacobson KA, Malorni W (1997) The A3 adenosine receptor mediates cell spreading, reorganization of actin cytoskeleton, and distribution of Bcl-XL: studies in human astroglioma cells. Biochem Biophys Res Commun 241:297–304PubMedGoogle Scholar
  646. 646.
    Abbracchio MP, Camurri A, Ceruti S, Cattabeni F, Falzano L, Giammarioli AM, Jacobson KA, Trincavelli L, Martini C, Malorni W, Fiorentini C (2001) The A3 adenosine receptor induces cytoskeleton rearrangement in human astrocytoma cells via a specific action on Rho proteins. Ann N Y Acad Sci 939:63–73PubMedGoogle Scholar
  647. 647.
    Trincavelli ML, Tuscano D, Marroni M, Falleni A, Gremigni V, Ceruti S, Abbracchio MP, Jacobson KA, Cattabeni F, Martini C (2002) A3 adenosine receptors in human astrocytoma cells: agonist-mediated desensitization, internalization, and down-regulation. Mol Pharmacol 62:1373–1384PubMedGoogle Scholar
  648. 648.
    Sai K, Yang D, Yamamoto H, Fujikawa H, Yamamoto S, Nagata T, Saito M, Yamamura T, Nishizaki T (2006) A1 adenosine receptor signal and AMPK involving caspase-9/-3 activation are responsible for adenosine-induced RCR-1 astrocytoma cell death. Neurotoxicology 27:458–467PubMedGoogle Scholar
  649. 649.
    Garcia-Gil M, Tozzi MG, Allegrini S, Folcarelli S, Della Sala G, Voccoli V, Colombaioni L, Camici M (2012) Novel metabolic aspects related to adenosine deaminase inhibition in a human astrocytoma cell line. Neurochem Int 60:523–532PubMedGoogle Scholar
  650. 650.
    Inoue K, Nakazawa K, Fujimori K, Takanaka A (1989) Extracellular adenosine 5′-triphosphate-evoked norepinephrine secretion not relating to voltage-gated Ca channels in pheochromocytoma PC12 cells. Neurosci Lett 106:294–299PubMedGoogle Scholar
  651. 651.
    Majid MA, Okajima F, Kondo Y (1992) Characterization of ATP receptor which mediates norepinephrine release in PC12 cells. Biochim Biophys Acta 1136:283–289PubMedGoogle Scholar
  652. 652.
    Hardwick JC, Ehrlich YH, Hendley ED (1989) Extracellular ATP stimulates norepinephrine uptake in PC12 cells. J Neurochem 53:1512–1518PubMedGoogle Scholar
  653. 653.
    Eshleman A, Dunigan C, Shamoo A, Eldefrawi M (1995) ATP enhances catecholamine uptake into PC12 cells. Life Sci 56:1613–1621PubMedGoogle Scholar
  654. 654.
    Nakazawa K, Fujimori K, Takanaka A, Inoue K (1990) An ATP-activated conductance in pheochromocytoma cells and its suppression by extracellular calcium. J Physiol 428:257–272PubMedPubMedCentralGoogle Scholar
  655. 655.
    Nakazawa K, Fujimori K, Takanaka A, Inoue K (1990) Reversible and selective antagonism by suramin of ATP-activated inward current in PC12 phaeochromocytoma cells. Br J Pharmacol 101:224–226PubMedPubMedCentralGoogle Scholar
  656. 656.
    Inoue K, Nakazawa K, Ohara-Imaizumi M, Obama T, Fujimori K, Takanaka A (1991) Selective and competitive antagonism by suramin of ATP-stimulated catecholamine-secretion from PC12 phaeochromocytoma cells. Br J Pharmacol 102:581–584PubMedPubMedCentralGoogle Scholar
  657. 657.
    Inoue K, Nakazawa K, Ohara-Imaizumi M, Obama T, Fujimori K, Takanaka A (1991) Antagonism by reactive blue 2 but not by brilliant blue G of extracellular ATP-evoked responses in PC12 phaeochromocytoma cells. Br J Pharmacol 102:851–854PubMedPubMedCentralGoogle Scholar
  658. 658.
    Sela D, Ram E, Atlas D (1991) ATP receptor. A putative receptor-operated channel in PC-12 cells. J Biol Chem 266:17990–17994PubMedGoogle Scholar
  659. 659.
    Nakazawa K, Fujimori K, Takanaka A, Inoue K (1991) Comparison of adenosine triphosphate- and nicotine-activated inward currents in rat phaeochromocytoma cells. J Physiol 434:647–660PubMedPubMedCentralGoogle Scholar
  660. 660.
    Majid MA, Okajima F, Kondo Y (1993) UTP activates phospholipase C-Ca2+ system through a receptor different from the 53-kDa ATP receptor in PC12 cells. Biochem Biophys Res Commun 195:415–421PubMedGoogle Scholar
  661. 661.
    Murrin RJ, Boarder MR (1992) Neuronal "nucleotide" receptor linked to phospholipase C and phospholipase D? Stimulation of PC12 cells by ATP analogues and UTP. Mol Pharmacol 41:561–568PubMedGoogle Scholar
  662. 662.
    Raha S, de Souza LR, Reed JK (1993) Intracellular signalling by nucleotide receptors in PC12 pheochromocytoma cells. J Cell Physiol 154:623–630PubMedGoogle Scholar
  663. 663.
    Barry VA, Cheek TR (1994) Extracellular ATP triggers two functionally distinct calcium signalling pathways in PC12 cells. J Cell Sci 107(Pt 2):451–462PubMedGoogle Scholar
  664. 664.
    Nikodijevic B, Sei Y, Shin Y, Daly JW (1994) Effects of ATP and UTP in pheochromocytoma PC12 cells: evidence for the presence of three P2 receptors, only one of which subserves stimulation of norepinephrine release. Cell Mol Neurobiol 14:27–47PubMedGoogle Scholar
  665. 665.
    de Souza LR, Moore H, Raha S, Reed JK (1995) Purine and pyrimidine nucleotides activate distinct signalling pathways in PC12 cells. J Neurosci Res 41:753–763PubMedGoogle Scholar
  666. 666.
    Michel AD, Grahames CB, Humphrey PP (1996) Functional characterisation of P2 purinoceptors in PC12 cells by measurement of radiolabelled calcium influx. Naunyn Schmiedebergs Arch Pharmacol 354:562–571PubMedGoogle Scholar
  667. 667.
    Nakazawa K, Ohno Y (1996) Dopamine and 5-hydroxytryptamine selectively potentiate neuronal type ATP receptor channels. Eur J Pharmacol 296:119–122PubMedGoogle Scholar
  668. 668.
    Koizumi S, Uneyama H, Ikeda M, Ueno S, Inoue K (1998) Inhibition by imipramine of ATP-evoked responses in rat pheochromocytoma cells. Biochem Biophys Res Commun 244:342–346PubMedGoogle Scholar
  669. 669.
    Kim HJ, Choi JS, Lee YM, Shim EY, Hong SH, Kim MJ, Min DS, Rhie DJ, Kim MS, Jo YH, Hahn SJ, Yoon SH (2005) Fluoxetine inhibits ATP-induced [Ca2+]i increase in PC12 cells by inhibiting both extracellular Ca2+ influx and Ca2+ release from intracellular stores. Neuropharmacology 49:265–274PubMedGoogle Scholar
  670. 670.
    Arslan G, Filipeanu CM, Irenius E, Kull B, Clementi E, Allgaier C, Erlinge D, Fredholm BB (2000) P2Y receptors contribute to ATP-induced increases in intracellular calcium in differentiated but not undifferentiated PC12 cells. Neuropharmacology 39:482–496PubMedGoogle Scholar
  671. 671.
    Hur EM, Park TJ, Kim KT (2001) Coupling of L-type voltage-sensitive calcium channels to P2X2 purinoceptors in PC-12 cells. Am J Physiol Cell Physiol 280:C1121–C1129PubMedGoogle Scholar
  672. 672.
    Tozaki-Saitoh H, Koizumi S, Sato Y, Tsuda M, Nagao T, Inoue K (2006) Retinoic acids increase P2X2 receptor expression through the 5′-flanking region of P2rx2 gene in rat phaeochromocytoma PC-12 cells. Mol Pharmacol 70:319–328PubMedGoogle Scholar
  673. 673.
    Liu PS, Hsieh HL, Lin CM (2001) Dehydroepiandrosterone sulfate (DHEAS) suppresses P2X purinoceptor-coupled responses in PC12 cells. Neurochem Int 39:193–198PubMedGoogle Scholar
  674. 674.
    Keath JR, Westhead EW (2004) Factors affecting habituation of PC12 cells to ATP. Eur J Biochem 271:4034–4041PubMedGoogle Scholar
  675. 675.
    Maruyama K, Ohta T, Ito S (2004) Involvement of mitochondrial Na+-Ca2+ exchange in intracellular Ca2+ increase induced by ATP in PC12 cells. Brain Res 1013:40–50PubMedGoogle Scholar
  676. 676.
    Marín-Vicente C, Gómez-Fernández JC, Corbalán-García S (2005) The ATP-dependent membrane localization of protein kinase C α is regulated by Ca2+ influx and phosphatidylinositol 4,5-bisphosphate in differentiated PC12 cells. Mol Biol Cell 16:2848–2861PubMedPubMedCentralGoogle Scholar
  677. 677.
    Sun JH, Cai GJ, Xiang ZH (2007) Expression of P2X purinoceptors in PC12 phaeochromocytoma cells. Clin Exp Pharmacol Physiol 34:1282–1286PubMedGoogle Scholar
  678. 678.
    Arthur DB, Taupenot L, Insel PA (2007) Nerve growth factor-stimulated neuronal differentiation induces changes in P2 receptor expression and nucleotide-stimulated catecholamine release. J Neurochem 100:1257–1264PubMedGoogle Scholar
  679. 679.
    Soltoff SP (1998) Related adhesion focal tyrosine kinase and the epidermal growth factor receptor mediate the stimulation of mitogen-activated protein kinase by the G-protein-coupled P2Y2 receptor. Phorbol ester or [Ca2+]i elevation can substitute for receptor activation. J Biol Chem 273:23110–23117PubMedGoogle Scholar
  680. 680.
    Xu H, Wu B, Jiang F, Xiong S, Zhang B, Li G, Liu S, Gao Y, Xu C, Tu G, Peng H, Liang S, Xiong H (2013) High fatty acids modulate P2X 7 expression and IL-6 release via the p38 MAPK pathway in PC12 cells. Brain Res Bull 94:63–70PubMedGoogle Scholar
  681. 681.
    Vartian N, Boehm S (2001) P2Y receptor-mediated inhibition of voltage-activated Ca2+ currents in PC12 cells. Eur J Neurosci 13:899–908PubMedGoogle Scholar
  682. 682.
    Kulick MB, von Kügelgen I (2002) P2Y-receptors mediating an inhibition of the evoked entry of calcium through N-type calcium channels at neuronal processes. J Pharmacol Exp Ther 303:520–526PubMedGoogle Scholar
  683. 683.
    Kubista H, Lechner SG, Wolf AM, Boehm S (2003) Attenuation of the P2Y receptor-mediated control of neuronal Ca2+ channels in PC12 cells by antithrombotic drugs. Br J Pharmacol 138:343–350PubMedPubMedCentralGoogle Scholar
  684. 684.
    Moskvina E, Unterberger U, Boehm S (2003) Activity-dependent autocrine-paracrine activation of neuronal P2Y receptors. J Neurosci 23:7479–7488PubMedGoogle Scholar
  685. 685.
    Hussl S, Kubista H, Boehm S (2007) Autoregulation in PC12 cells via P2Y receptors: evidence for non-exocytotic nucleotide release from neuroendocrine cells. Purinergic Signal 3:367–375PubMedPubMedCentralGoogle Scholar
  686. 686.
    Daniele S, Lecca D, Trincavelli ML, Ciampi O, Abbracchio MP, Martini C (2010) Regulation of PC12 cell survival and differentiation by the new P2Y-like receptor GPR17. Cell Signal 22:697–706PubMedGoogle Scholar
  687. 687.
    Marín-Vicente C, Guerrero-Valero M, Nielsen ML, Savitski MM, Gómez-Fernández JC, Zubarev RA, Corbalán-García S (2011) ATP enhances neuronal differentiation of PC12 cells by activating PKCα interactions with cytoskeletal proteins. J Proteome Res 10:529–540PubMedGoogle Scholar
  688. 688.
    Prasai P, Stefos GC, Becker W (2011) Extracellular ATP activates NFAT-dependent gene expression in neuronal PC12 cells via P2X receptors. BMC Neurosci 12:90PubMedPubMedCentralGoogle Scholar
  689. 689.
    Erny RE, Berezo MW, Perlman RL (1981) Activation of tyrosine 3-monooxygenase in pheochromocytoma cells by adenosine. J Biol Chem 256:1335–1339PubMedGoogle Scholar
  690. 690.
    Erny R, Wagner JA (1984) Adenosine-dependent activation of tyrosine hydroxylase is defective in adenosine kinase-deficient PC12 cells. Proc Natl Acad Sci U S A 81:4974–4978PubMedPubMedCentralGoogle Scholar
  691. 691.
    Rabe CS, McGee R Jr (1983) Regulation of depolarization-dependent release of neurotransmitters by adenosine: cyclic AMP-dependent enhancement of release from PC12 cells. J Neurochem 41:1623–1634PubMedGoogle Scholar
  692. 692.
    Wu N, Armstrong I, Wagner J (1984) Genetic evidence that chloroadenosine increases the specific activity of choline acetyltransferase in PC12 cells via modulation of an adenosine-dependent adenylate cyclase. Neuroscience 13:1365–1371PubMedGoogle Scholar
  693. 693.
    Williams M, Abreu M, Jarvis MF, Noronha-Blob L (1987) Characterization of adenosine receptors in the PC12 pheochromocytoma cell line using radioligand binding: evidence for A-2 selectivity. J Neurochem 48:498–502PubMedGoogle Scholar
  694. 694.
    Hide I, Padgett WL, Jacobson KA, Daly JW (1992) A2A adenosine receptors from rat striatum and rat pheochromocytoma PC12 cells: characterization with radioligand binding and by activation of adenylate cyclase. Mol Pharmacol 41:352–359PubMedGoogle Scholar
  695. 695.
    Chern Y, Lai HL, Fong JC, Liang Y (1993) Multiple mechanisms for desensitization of A2a adenosine receptor-mediated cAMP elevation in rat pheochromocytoma PC12 cells. Mol Pharmacol 44:950–958PubMedGoogle Scholar
  696. 696.
    Park TJ, Song SK, Kim KT (1997) A2A adenosine receptors inhibit ATP-induced Ca2+ influx in PC12 cells by involving protein kinase A. J Neurochem 68:2177–2185PubMedGoogle Scholar
  697. 697.
    Kobayashi S, Beitner-Johnson D, Conforti L, Millhorn DE (1998) Chronic hypoxia reduces adenosine A2A receptor-mediated inhibition of calcium current in rat PC12 cells via downregulation of protein kinase A. J Physiol 512:351–363PubMedPubMedCentralGoogle Scholar
  698. 698.
    O’Driscoll CM, Gorman AM (2005) Hypoxia induces neurite outgrowth in PC12 cells that is mediated through adenosine A2A receptors. Neuroscience 131:321–329PubMedGoogle Scholar
  699. 699.
    Loeffler DA, Camp DM, Juneau PL, Harel E, LeWitt PA (2000) Purine-induced alterations of dopamine metabolism in rat pheochromocytoma PC12 cells. Brain Res Bull 52:553–558PubMedGoogle Scholar
  700. 700.
    Thevananther S, Rivera A, Rivkees SA (2001) A1 adenosine receptor activation inhibits neurite process formation by Rho kinase-mediated pathways. Neuroreport 12:3057–3063PubMedGoogle Scholar
  701. 701.
    Charles MP, Adamski D, Kholler B, Pelletier L, Berger F, Wion D (2003) Induction of neurite outgrowth in PC12 cells by the bacterial nucleoside N6-methyldeoxyadenosine is mediated through adenosine A2a receptors and via cAMP and MAPK signaling pathways. Biochem Biophys Res Commun 304:795–800PubMedGoogle Scholar
  702. 702.
    Trincavelli ML, Falleni A, Chelli B, Tuscano D, Costa B, Gremigni V, Lucacchini A, Martini C (2003) A2A adenosine receptor ligands and proinflammatory cytokines induce PC 12 cell death through apoptosis. Biochem Pharmacol 66:1953–1962PubMedGoogle Scholar
  703. 703.
    Lu MK, Cheng JJ, Lai WL, Lin YR, Huang NK (2006) Adenosine as an active component of Antrodia cinnamomea that prevents rat PC12 cells from serum deprivation-induced apoptosis through the activation of adenosine A2A receptors. Life Sci 79:252–258PubMedGoogle Scholar
  704. 704.
    Hattori N, Nomoto H, Mishima S, Inagaki S, Goto M, Sako M, Furukawa S (2006) Identification of AMP N 1-oxide in royal jelly as a component neurotrophic toward cultured rat pheochromocytoma PC12 cells. Biosci Biotechnol Biochem 70:897–906PubMedGoogle Scholar
  705. 705.
    Koizumi S, Watano T, Nakazawa K, Inoue K (1994) Potentiation by adenosine of ATP-evoked dopamine release via a pertussis toxin-sensitive mechanism in rat phaeochromocytoma PC12 cells. Br J Pharmacol 112:992–997PubMedPubMedCentralGoogle Scholar
  706. 706.
    Nakazawa K, Inoue K, Koizumi S, Inoue K (1994) Facilitation by 5-hydroxytryptamine of ATP-activated current in rat pheochromocytoma cells. Pflugers Arch 427:492–499PubMedGoogle Scholar
  707. 707.
    Koizumi S, Ikeda M, Inoue K, Nakazawa K, Inoue K (1995) Enhancement by zinc of ATP-evoked dopamine release from rat pheochromocytoma PC12 cells. Brain Res 673:75–82PubMedGoogle Scholar
  708. 708.
    Ikeda M, Koizumi S, Nakazawa K, Inoue K, Ito K, Inoue K (1996) Potentiation by cadmium ion of ATP-evoked dopamine release in rat phaeochromocytoma cells. Br J Pharmacol 117:950–954PubMedPubMedCentralGoogle Scholar
  709. 709.
    Nakazawa K, Ito K, Koizumi S, Ohno Y, Inoue K (1995) Reduction of acetylcholine-activated current by low concentrations of extracellular adenosine 5′-triphosphate. Life Sci 57:L351–L356Google Scholar
  710. 710.
    Murayama T, Oda H, Watanabe A, Nomura Y (1995) ATP receptor-mediated increase of Ca ionophore-stimulated arachidonic acid release from PC12 pheochromocytoma cells. Jpn J Pharmacol 69:43–51PubMedGoogle Scholar
  711. 711.
    Nordone AJ, Pivorun EB (1995) Cytosolic calcium responses to extracellular adenosine 5',5" '-P1,P4-tetraphosphate in PC12 cells. Pharmacol Biochem Behav 52:85–91PubMedGoogle Scholar
  712. 712.
    Shoji-Kasai Y, Yoshida A, Sato K, Hoshino T, Ogura A, Kondo S, Fujimoto Y, Kuwahara R, Kato R, Takahashi M (1992) Neurotransmitter release from synaptotagmin-deficient clonal variants of PC12 cells. Science 256:1821–1823PubMedGoogle Scholar
  713. 713.
    Fujimori H, Yasuda M, Pan-Hou H (2002) Enhancement of cellular adenosine triphosphate levels in PC12 cells by extracellular adenosine. Biol Pharm Bull 25:307–311PubMedGoogle Scholar
  714. 714.
    Lechner SG, Dorostkar MM, Mayer M, Edelbauer H, Pankevych H, Boehm S (2004) Autoinhibition of transmitter release from PC12 cells and sympathetic neurons through a P2Y12 receptor-mediated inhibition of voltage-gated Ca2+ channels. Eur J Neurosci 20:2917–2928PubMedGoogle Scholar
  715. 715.
    Fabbro A, Skorinkin A, Grandolfo M, Nistri A, Giniatullin R (2004) Quantal release of ATP from clusters of PC12 cells. J Physiol 560:505–517PubMedPubMedCentralGoogle Scholar
  716. 716.
    Fujimori H, Pan-Hou H (2005) Enhancement of cellular adenosine triphosphate levels in PC12 cells by 2,5-dideoxyadenosine, a P-site inhibitor of adenylate cyclase. Biol Pharm Bull 28:358–360PubMedGoogle Scholar
  717. 717.
    Gardner A, Westfall TC, Macarthur H (2005) Endothelin (ET)-1-induced inhibition of ATP release from PC-12 cells is mediated by the ETB receptor: differential response to ET-1 on ATP, neuropeptide Y, and dopamine levels. J Pharmacol Exp Ther 313:1109–1117PubMedGoogle Scholar
  718. 718.
    Yamboliev IA, Smyth LM, Durnin L, Dai Y, Mutafova-Yambolieva VN (2009) Storage and secretion of β-NAD, ATP and dopamine in NGF-differentiated rat pheochromocytoma PC12 cells. Eur J Neurosci 30:756–768PubMedPubMedCentralGoogle Scholar
  719. 719.
    Richter-Landsberg C, Maronde E, Besser AS (1993) Ecto-5′-nucleotidase activity in PC 12 cells is synergistically modulated by nerve growth factor and 8-bromo-cAMP. Neurosci Res Comm 12:51–54Google Scholar
  720. 720.
    Heilbronn A, Maienschein V, Carstensen K, Gann W, Zimmermann H (1995) Crucial role of ecto-5′-nucleotidase in differentiation and survival of developing neural cells. Neuroreport 7:257–261PubMedGoogle Scholar
  721. 721.
    Cheng Y, Chen M, James-Kracke M, Wixom P, Sun AY (1996) Enhanced lipid peroxidation by extracellular ATP in PC12 cells. Neurochem Res 21:27–33PubMedGoogle Scholar
  722. 722.
    Gysbers JW, Rathbone MP (1996) GTP and guanosine synergistically enhance NGF-induced neurite outgrowth from PC12 cells. Int J Dev Neurosci 14:19–34PubMedGoogle Scholar
  723. 723.
    Gysbers JW, Guarnieri S, Mariggiò MA, Pietrangelo T, Fanò G, Rathbone MP (2000) Extracellular guanosine 5′ triphosphate enhances nerve growth factor-induced neurite outgrowth via increases in intracellular calcium. Neuroscience 96:817–824PubMedGoogle Scholar
  724. 724.
    Guarnieri S, Fanò G, Rathbone MP, Mariggiò MA (2004) Cooperation in signal transduction of extracellular guanosine 5′ triphosphate and nerve growth factor in neuronal differentiation of PC12 cells. Neuroscience 128:697–712PubMedGoogle Scholar
  725. 725.
    Bau C, Middlemiss PJ, Hindley S, Jiang S, Ciccarelli R, Caciagli F, Diiorio P, Werstiuk ES, Rathbone MP (2005) Guanosine stimulates neurite outgrowth in PC12 cells via activation of heme oxygenase and cyclic GMP. Purinergic Signal 1:161–172PubMedPubMedCentralGoogle Scholar
  726. 726.
    Chen Y, Sun AY (1998) Activation of transcription factor AP-1 by extracellular ATP in PC12 cells. Neurochem Res 23:543–550PubMedGoogle Scholar
  727. 727.
    Fujita N, Kakimi M, Ikeda Y, Hiramoto T, Suzuki K (2000) Extracellular ATP inhibits starvation-induced apoptosis via P2X2 receptors in differentiated rat pheochromocytoma PC12 cells. Life Sci 66:1849–1859PubMedGoogle Scholar
  728. 728.
    Schindelholz B, Reber BF (2000) L-type Ca2+ channels and purinergic P2X2 cation channels participate in calcium-tyrosine kinase-mediated PC12 growth cone arrest. Eur J Neurosci 12:194–204PubMedGoogle Scholar
  729. 729.
    Pooler AM, Guez DH, Benedictus R, Wurtman RJ (2005) Uridine enhances neurite outgrowth in nerve growth factor-differentiated PC12 [corrected]. Neuroscience 134:207–214PubMedGoogle Scholar
  730. 730.
    Belliveau DJ, Bani-Yaghoub M, McGirr B, Naus CC, Rushlow WJ (2006) Enhanced neurite outgrowth in PC12 cells mediated by connexin hemichannels and ATP. J Biol Chem 281:20920–20931PubMedGoogle Scholar
  731. 731.
    D’Ambrosi N, Cavaliere F, Merlo D, Milazzo L, Mercanti D, Volonté C (2000) Antagonists of P2 receptor prevent NGF-dependent neuritogenesis in PC12 cells. Neuropharmacology 39:1083–1094PubMedGoogle Scholar
  732. 732.
    D’Ambrosi N, Murra B, Cavaliere F, Amadio S, Bernardi G, Burnstock G, Volonté C (2001) Interaction between ATP and nerve growth factor signalling in the survival and neuritic outgrowth from PC12 cells. Neuroscience 108:527–534PubMedGoogle Scholar
  733. 733.
    Behrsing HP, Vulliet PR (2004) Mitogen-activated protein kinase mediates purinergic-enhanced nerve growth factor-induced neurite outgrowth in PC12 cells. J Neurosci Res 78:64–74PubMedGoogle Scholar
  734. 734.
    Lee CS, Bae YS, Lee SD, Suh PG, Ryu SH (2001) ATP-induced mitogenesis is modulated by phospholipase D2 through extracellular signal regulated protein kinase dephosphorylation in rat pheochromocytoma PC12 cells. Neurosci Lett 313:117–120PubMedGoogle Scholar
  735. 735.
    D’Ambrosi N, Costanzi S, Angelini DF, Volpini R, Sancesario G, Cristalli G, Volonté C (2004) 2-ClATP exerts anti-tumoural actions not mediated by P2 receptors in neuronal and glial cell lines. Biochem Pharmacol 67:621–630PubMedGoogle Scholar
  736. 736.
    Homma K, Niino Y, Hotta K, Oka K (2008) Ca2+ influx through P2X receptors induces actin cytoskeleton reorganization by the formation of cofilin rods in neurites. Mol Cell Neurosci 37:261–270PubMedGoogle Scholar
  737. 737.
    Sato A, Arimura Y, Manago Y, Nishikawa K, Aoki K, Wada E, Suzuki Y, Osaka H, Setsuie R, Sakurai M, Amano T, Aoki S, Wada K, Noda M (2006) Parkin potentiates ATP-induced currents due to activation of P2X receptors in PC12 cells. J Cell Physiol 209:172–182PubMedGoogle Scholar
  738. 738.
    Liu PS, Chen YY (2006) Butyl benzyl phthalate blocks Ca2+ signaling coupled with purinoceptor in rat PC12 cells. Toxicol Appl Pharmacol 210:136–141PubMedGoogle Scholar
  739. 739.
    Liu PS, Chiung YM, Kao YY, Chen HT (2006) 2,4-Toluene diisocyanate suppressed the calcium signaling of ligand gated ion channel receptors. Toxicology 219:167–174PubMedGoogle Scholar
  740. 740.
    Mantyh PW, Clohisy DR, Koltzenburg M, Hunt SP (2002) Molecular mechanisms of cancer pain. Nat Rev Cancer 2:201–209PubMedGoogle Scholar
  741. 741.
    Nagamine K, Ozaki N, Shinoda M, Asai H, Nishiguchi H, Mitsudo K, Tohnai I, Ueda M, Sugiura Y (2006) Mechanical allodynia and thermal hyperalgesia induced by experimental squamous cell carcinoma of the lower gingiva in rats. J Pain 7:659–670PubMedGoogle Scholar
  742. 742.
    Chizhmakov I, Yudin Y, Mamenko N, Prudnikov I, Tamarova Z, Krishtal O (2005) Opioids inhibit purinergic nociceptors in the sensory neurons and fibres of rat via a G protein-dependent mechanism. Neuropharmacology 48:639–647PubMedGoogle Scholar
  743. 743.
    Fujita M, Andoh T, Sasaki A, Saiki I, Kuraishi Y (2010) Involvement of peripheral adenosine 5′-triphosphate and P2X purinoceptor in pain-related behavior produced by orthotopic melanoma inoculation in mice. Eur J Neurosci 31:1629–1636PubMedGoogle Scholar
  744. 744.
    Kaan TK, Yip PK, Patel S, Davies M, Marchand F, Cockayne DA, Nunn PA, Dickenson AH, Ford AP, Zhong Y, Malcangio M, McMahon SB (2010) Systemic blockade of P2X3 and P2X2/3 receptors attenuates bone cancer pain behaviour in rats. Brain 133:2549–2564PubMedGoogle Scholar
  745. 745.
    Hansen RR, Nasser A, Falk S, Baldvinsson SB, Ohlsson PH, Bahl JM, Jarvis MF, Ding M, Heegaard AM (2012) Chronic administration of the selective P2X3, P2X2/3 receptor antagonist, A-317491, transiently attenuates cancer-induced bone pain in mice. Eur J Pharmacol 688:27–34PubMedGoogle Scholar
  746. 746.
    Falk S, Uldall M, Heegaard AM (2012) The role of purinergic receptors in cancer-induced bone pain. J Osteoporos 2012:758181PubMedPubMedCentralGoogle Scholar
  747. 747.
    Ye Y, Dang D, Viet CT, Dolan JC, Schmidt BL (2012) Analgesia targeting IB4-positive neurons in cancer-induced mechanical hypersensitivity. J Pain 13:524–531PubMedPubMedCentralGoogle Scholar
  748. 748.
    Hansen RR, Nielsen CK, Nasser A, Thomsen SI, Eghorn LF, Pham Y, Schulenburg C, Syberg S, Ding M, Stojilkovic SS, Jorgensen NR, Heegaard AM (2011) P2X7 receptor-deficient mice are susceptible to bone cancer pain. Pain 152:1766–1776PubMedGoogle Scholar
  749. 749.
    Chen J, Wang L, Zhang Y, Yang J (2012) P2Y1 purinoceptor inhibition reduces extracellular signal-regulated protein kinase 1/2 phosphorylation in spinal cord and dorsal root ganglia: implications for cancer-induced bone pain. Acta Biochim Biophys Sin (Shanghai) 44:367–372Google Scholar
  750. 750.
    Pellegatti P, Falzoni S, Pinton P, Rizzuto R, Di Virgilio F (2005) A novel recombinant plasma membrane-targeted luciferase reveals a new pathway for ATP secretion. Mol Biol Cell 16:3659–3665PubMedPubMedCentralGoogle Scholar
  751. 751.
    Adinolfi E, Raffaghello L, Giuliani AL, Cavazzini L, Capece M, Chiozzi P, Bianchi G, Kroemer G, Pistoia V, Di Virgilio F (2012) Expression of P2X7 receptor increases in vivo tumor growth. Cancer Res 72:2957–2969PubMedGoogle Scholar
  752. 752.
    Roger S, Pelegrin P (2011) P2X7 receptor antagonism in the treatment of cancers. Expert Opin Investig Drugs 20:875–880PubMedGoogle Scholar
  753. 753.
    Gorodeski GI (2012) P2X7 receptors and epithelial cancers. WIREs Membr Transp Signal 1:349–371Google Scholar
  754. 754.
    Blay J, White TD, Hoskin DW (1997) The extracellular fluid of solid carcinomas contains immunosuppressive concentrations of adenosine. Cancer Res 57:2602–2605PubMedGoogle Scholar
  755. 755.
    Ghiringhelli F, Bruchard M, Chalmin F, Rébe C (2012) Production of adenosine by ectonucleotidases: a key factor in tumor immunoescape. J Biomed Biotechnol 2012:473712PubMedPubMedCentralGoogle Scholar
  756. 756.
    Clayton A, Al-Taei S, Webber J, Mason MD, Tabi Z (2011) Cancer exosomes express CD39 and CD73, which suppress T cells through adenosine production. J Immunol 187:676–683PubMedGoogle Scholar
  757. 757.
    Mandapathil M, Whiteside TL (2011) Targeting human inducible regulatory T cells (Tr1) in patients with cancer: blocking of adenosine-prostaglandin E2 cooperation. Expert Opin Biol Ther 11:1203–1214PubMedPubMedCentralGoogle Scholar
  758. 758.
    Zhang B (2012) Opportunities and challenges for anti-CD73 cancer therapy. Immunotherapy 4:861–865PubMedGoogle Scholar
  759. 759.
    Garg AD, Krysko DV, Verfaillie T, Kaczmarek A, Ferreira GB, Marysael T, Rubio N, Firczuk M, Mathieu C, Roebroek AJ, Annaert W, Golab J, de Witte P, Vandenabeele P, Agostinis P (2012) A novel pathway combining calreticulin exposure and ATP secretion in immunogenic cancer cell death. EMBO J 31:1062–1079PubMedPubMedCentralGoogle Scholar
  760. 760.
    Beavis PA, Stagg J, Darcy PK, Smyth MJ (2012) CD73: a potent suppressor of antitumor immune responses. Trends Immunol 33:231–237PubMedGoogle Scholar
  761. 761.
    Waickman AT, Alme A, Senaldi L, Zarek PE, Horton M, Powell JD (2012) Enhancement of tumor immunotherapy by deletion of the A2A adenosine receptor. Cancer Immunol Immunother 61:917–926PubMedPubMedCentralGoogle Scholar
  762. 762.
    Cekic C, Sag D, Linden J (2012) Cell-intrinsic adenosine A2A receptor signalling is required for T cell homeostasis and control of tumor growth b. J Immunol 188:47.1Google Scholar
  763. 763.
    Cekic C, Linden J (2012) Adenosine A2B receptor signalling in antigen presenting cells suppress anti-tumor adaptive immune responses. J Immunol 188:127.10Google Scholar
  764. 764.
    Stagg J, Divisekera U, Duret H, Sparwasser T, Teng MW, Darcy PK, Smyth MJ (2011) CD73-deficient mice have increased antitumor immunity and are resistant to experimental metastasis. Cancer Res 71:2892–2900PubMedGoogle Scholar
  765. 765.
    MacKenzie WM, Hoskin DW, Blay J (1994) Adenosine inhibits the adhesion of anti-CD3-activated killer lymphocytes to adenocarcinoma cells through an A3 receptor. Cancer Res 54:3521–3526PubMedGoogle Scholar
  766. 766.
    Lin K, Lin J, Wu WI, Ballard J, Lee BB, Gloor SL, Vigers GP, Morales TH, Friedman LS, Skelton N, Brandhuber BJ (2012) An ATP-site on-off switch that restricts phosphatase accessibility of Akt b. Sci Signal 5:ra37PubMedGoogle Scholar
  767. 767.
    Cheng Y, Senthamizhchelvan S, Agarwal R, Green GM, Mease RC, Sgouros G, Huso DL, Pomper MG, Meltzer SJ, Abraham JM (2012) [32P]ATP inhibits the growth of xenografted tumors in nude mice. Cell Cycle 11:1878–1882PubMedPubMedCentralGoogle Scholar
  768. 768.
    Gaspar A, Silver T, Borges F (2011) Adenosine A3 receptors: a new therapeutic approach in cancer. Química Nova 34:1417–1424Google Scholar
  769. 769.
    Manga K, Serban G, Schwartz J, Slotky R, Patel N, Fan J, Bai X, Chari A, Savage D, Suciu-Foca N, Colovai AI (2010) Increased adenosine triphosphate production by peripheral blood CD4+ cells in patients with hematologic malignancies treated with stem cell mobilization agents. Hum Immunol 71:652–658PubMedGoogle Scholar
  770. 770.
    Zadran S, Sanchez D, Zadran H, Amighi A, Otiniano E, Wong K (2013) Enhanced-acceptor fluorescence-based single cell ATP biosensor monitors ATP in heterogeneous cancer populations in real time. Biotechnol Lett 35:175–180PubMedGoogle Scholar
  771. 771.
    Coutinho-Silva R, Stahl L, Cheung K-K, Ojcius DC, Burnstock G (2005) P2X and P2Y purinergic receptors on human intestinal epithelial carcinoma cell lines: effects of extracellular nucleotides on apoptosis and cell proliferation. Am J Physiol Gastrointest Liver Physiol 288:G1024–G1035PubMedGoogle Scholar
  772. 772.
    Di Virgilio F, Borea PA, Illes P (2001) P2 receptors meet the immune system. Trends Pharmacol Sci 22:5–7PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  1. 1.Autonomic Neuroscience CentreUniversity College Medical SchoolLondonUK
  2. 2.Department of PharmacologyThe University of MelbourneMelbourneAustralia
  3. 3.Dipartimento di Morfologia, Chirurgia e Medicina SperimentaleUniversità degli Studi di FerraraFerraraItaly

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