Skip to main content

Advertisement

SpringerLink
Log in

Effects of Lysophospholipids on Tumor Microenvironment

  • Original Paper
  • Published:
Cancer Microenvironment

Abstract

The effects of lysophospholipids (LPLs) on cancer microenvironment is a vast and growing field. These lipids are secreted physiologically by various cell types. They play highly important roles in the development, activation and regulation of the immune system. They are also secreted by cancerous cells and there is a strong association between LPLs and cancer. It is clear that these lipids and in particular sphingosine 1-phosphate (S1P) and lysophosphatidic acid (LPA) play major roles in regulating the growth of tumor cells, and in manipulating the immune system. These activities can be divided into two parts; the first involves the ability of S1P and LPA to either directly or through some of the enzymes that generate them such as sphingosine kinases or phospholipases, induce the motility and invasiveness of tumor cells. The second mechanism involves the recently discovered effects of these lipids on the anti-tumor effector natural killer (NK) cells. Whereas S1P and LPA induce the recruitment of these effector cells, they also inhibit their cytolysis of tumor cells. This may support the environment of cancer and the ability of cancer cells to grow, spread and metastasize. Consequently, LPLs or their receptors may be attractive targets for developing drugs in the treatment of cancer where LPLs or their receptors are up-regulated.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Chun J, Goetzl EJ, Hla T et al (2008) International union of pharmacology. XXXIV. Lysophospholipid receptor nomenclature. Pharmacol Rev 54:265–269

    Article  Google Scholar 

  2. Rivera R, Chun J (2008) Biological effects of lysophospholipids. Rev Physiol Biochem Pharmacol 160:25–46

    Article  PubMed  CAS  Google Scholar 

  3. Choi JW, Herr DR, Noguchi K et al (2010) LPA receptors: subtypes and biological actions. Annu Rev Pharmacol Toxicol 50:157–186

    Article  PubMed  CAS  Google Scholar 

  4. Maghazachi AA (2005) Insights into seven and single transmembrane-spanning domain receptors and their signaling pathways in human natural killer cells. Pharmacol Rev 57:339–357

    Article  PubMed  CAS  Google Scholar 

  5. Cinque B, Di ML, Centi C et al (2003) Sphingolipids and the immune system. Pharmacol Res 47:421–437

    Article  PubMed  CAS  Google Scholar 

  6. Mills GB, Moolenaar WH (2003) The emerging role of lysophosphatidic acid in cancer. Nat Rev Cancer 3:582–591

    Article  PubMed  CAS  Google Scholar 

  7. Tigyi G, Dyer DL, Miledi R (1994) Lysophosphatidic acid possesses dual action in cell proliferation. Proc Natl Acad Sci USA 91:1908–1912

    Article  PubMed  CAS  Google Scholar 

  8. Sengupta S, Xiao YJ, Xu Y (2003) A novel laminin-induced LPA autocrine loop in the migration of ovarian cancer cells. FASEB J 17:1570–1572

    PubMed  CAS  Google Scholar 

  9. Sengupta S, Kim KS, Berk MP et al (2007) Lysophosphatidic acid downregulates tissue inhibitor of metalloproteinases, which are negatively involved in lysophosphatidic acid-induced cell invasion. Oncogene 26:2894–2901

    Article  PubMed  CAS  Google Scholar 

  10. Kim KS, Sengupta S, Berk M et al (2006) Hypoxia enhances lysophosphatidic acid responsiveness in ovarian cancer cells and lysophosphatidic acid induces ovarian tumor metastasis in vivo. Cancer Res 66:7983–7990

    Article  PubMed  CAS  Google Scholar 

  11. Xu Y, Shen Z, Wiper DW et al (1998) Lysophosphatidic acid as a potential biomarker for ovarian and other gynecologic cancers. JAMA 280:719–723

    Article  PubMed  CAS  Google Scholar 

  12. Sedláková I, Vávrová J, Tošner J, Hanousek L (2010) Lysophosphatidic acid in patients with ovarian cancer. Clin Ovarian Cancer 3:41–46

    Article  CAS  Google Scholar 

  13. Masuda A, Nakamura K, Izutsu K et al (2008) Serum autotaxin measurement in haematological malignancies: a promising marker for follicular lymphoma. Br J Haematol 143:60–70

    Article  PubMed  CAS  Google Scholar 

  14. Sano T, Baker D, Virag T, Wada A et al (2002) Multiple mechanisms linked to platelet activation result in lysophosphatidic acid and sphingosine 1-phosphate generation in blood. J Biol Chem 277:21197–21206

    Article  PubMed  CAS  Google Scholar 

  15. Yatomi Y, Ohmori T, Rile G et al (2009) Sphingosine 1-phosphate as a major bioactive lysophospholipid that is released from platelets and interacts with endothelial cells. Blood 96:3431–3438

    Google Scholar 

  16. Yatomi Y, Ozaki Y, Ohmori T, Igarashi Y (2001) Sphingosine 1-phosphate: synthesis and release. Prostaglandins 64:107–122

    PubMed  CAS  Google Scholar 

  17. Yang L, Yatomi Y, Miura Y et al (1999) Metabolism and functional effects of sphingolipids in blood cells. Br J Haematol 107:282–293

    Article  PubMed  CAS  Google Scholar 

  18. Kim RH, Takabe K, Milstien S, Spiegel S (2009) Export and functions of sphingosine-1-phosphate. Biochim Biophys Acta 1791:692–696

    PubMed  CAS  Google Scholar 

  19. Xu Y, Fang XJ, Casey G, Mills GB (1995) Lysophospholipids activate ovarian and breast cancer cells. Biochem J 309:933–940

    PubMed  CAS  Google Scholar 

  20. Spiegel S, Milstien S (2004) Sphingosine-1-phosphate: signaling inside and out. FEBS Lett 476:55–57

    Article  Google Scholar 

  21. Rivera J, Proia RL, Olivera A (2008) The alliance of sphingosine-1-phosphate and its receptors in immunity. Nat Rev Immunol 8:753–763

    Article  PubMed  CAS  Google Scholar 

  22. Pyne S, Pyne NJ (2000) Sphingosine 1-phosphate signalling in mammalian cells. Biochem J 349:385–402

    Article  PubMed  CAS  Google Scholar 

  23. Okazaki T, Bell RM, Hannun YA (1989) Sphingomyelin turnover induced by vitamin D3 in HL-60 cells. Role in cell differentiation. J Biol Chem 264:19076–19080

    PubMed  CAS  Google Scholar 

  24. Hannun YA, Obeid LM (2008) Principles of bioactive lipid signalling: lessons from sphingolipids. Nat Rev Mol Cell Biol 9:139–150

    Article  PubMed  CAS  Google Scholar 

  25. Mechtcheriakova D, Wlachos A, Sobanov J et al (2007) Sphingosine 1-phosphate phosphatase 2 is induced during inflammatory responses. Cell Signal 19:748–760

    Article  PubMed  CAS  Google Scholar 

  26. Peest U, Sensken SC, Andreani P et al (2008) S1P-lyase independent clearance of extracellular sphingosine 1-phosphate after dephosphorylation and cellular uptake. J Cell Biochem 104:756–772

    Article  PubMed  CAS  Google Scholar 

  27. Zhao Y, Kalari SK, Usatyuk PV et al (2007) Intracellular generation of sphingosine 1-phosphate in human lung endothelial cells: role of lipid phosphate phosphatase-1 and sphingosine kinase 1. J Biol Chem 282:14165–14177

    Article  PubMed  CAS  Google Scholar 

  28. Schwab SR, Pereira JP, Matloubian M et al (2005) Lymphocyte sequestration through S1P lyase inhibition and disruption of S1P gradients. Science 309:1735–1739

    Article  PubMed  CAS  Google Scholar 

  29. Venkataraman K, Lee YM, Michaud J et al (2008) Vascular endothelium as a contributor of plasma sphingosine 1-phosphate. Circ Res 102:669–676

    Article  PubMed  CAS  Google Scholar 

  30. Pappu R, Schwab SR, Cornelissen I et al (2007) Promotion of lymphocyte egress into blood and lymph by distinct sources of sphingosine-1-phosphate. Science 316:295–298

    Article  PubMed  CAS  Google Scholar 

  31. Hanel P, Andreani P, Graler MH (2007) Erythrocytes store and release sphingosine 1-phosphate in blood. FASEB J 21:1202–1209

    Article  PubMed  CAS  Google Scholar 

  32. Hla T (2004) Physiological and pathological actions of sphingosine 1-phosphate. Semin Cell Dev Biol 15:513–520

    Article  PubMed  CAS  Google Scholar 

  33. Taha TA, Hannun YA, Obeid LM (2006) Sphingosine kinase: biochemical and cellular regulation and role in disease. J Biochem Mol Biol 39:113–131

    Article  PubMed  CAS  Google Scholar 

  34. Goetzl EJ, Kong Y, Mei B (1999) Lysophosphatidic acid and sphingosine 1-phosphate protection of T cells from apoptosis in association with suppression of Bax. J Immunol 162:2049–2056

    PubMed  CAS  Google Scholar 

  35. Xia P, Gamble JR, Wang L et al (2000) An oncogenic role of sphingosine kinase. Curr Biol 10:1527–1530

    Article  PubMed  CAS  Google Scholar 

  36. Taha TA, Kitatani K, El-Alwani M et al (2006) Loss of sphingosine kinase-1 activates the intrinsic pathway of programmed cell death: modulation of sphingolipid levels and the induction of apoptosis. FASEB J 20:482–484

    PubMed  CAS  Google Scholar 

  37. Kawamori T, Osta W, Johnson KR et al (2006) Sphingosine kinase 1 is up-regulated in colon carcinogenesis. FASEB J 20:386–388

    PubMed  CAS  Google Scholar 

  38. French KJ, Upson JJ, Keller SN et al (2006) Antitumor activity of sphingosine kinase inhibitors. J Pharmacol Exp Ther 318:596–603

    Article  PubMed  CAS  Google Scholar 

  39. French KJ, Schrecengost RS, Lee BD et al (2003) Discovery and evaluation of inhibitors of human sphingosine kinase. Cancer Res 63:5962–5969

    PubMed  CAS  Google Scholar 

  40. Sankala HM, Hait NC, Paugh SW et al (2007) Involvement of sphingosine kinase 2 in p53-independent induction of p21 by the chemotherapeutic drug doxorubicin. Cancer Res 67:10466–10474

    Article  PubMed  CAS  Google Scholar 

  41. Van Brocklyn JR, Jackson CA, Pearl DK et al (2005) Sphingosine kinase-1 expression correlates with poor survival of patients with glioblastoma multiforme: roles of sphingosine kinase isoforms in growth of glioblastoma cell lines. J Neuropathol Exp Neurol 64:695–705

    Article  PubMed  Google Scholar 

  42. Van Brocklyn JR, Young N, Roof R (2003) Sphingosine-1-phosphate stimulates motility and invasiveness of human glioblastoma multiforme cells. Cancer Lett 199:53–60

    Article  PubMed  CAS  Google Scholar 

  43. Yoshida Y, Nakada M, Sugimoto N et al (2010) Sphingosine-1-phosphate receptor type 1 regulates glioma cell proliferation and correlates with patient survival. Int J Cancer 126:2341–2352

    PubMed  CAS  Google Scholar 

  44. Jaillard C, Harrison S, Stankoff B et al (2005) Edg8/S1P5: an oligodendroglial receptor with dual function on process retraction and cell survival. J Neurosci 25:1459–1469

    Article  PubMed  CAS  Google Scholar 

  45. Young N, Van Brocklyn JR (2007) Roles of sphingosine-1-phosphate (S1P) receptors in malignant behavior of glioma cells. Differential effects of S1P2 on cell migration and invasiveness. Exp Cell Res 313:1615–1627

    Article  PubMed  CAS  Google Scholar 

  46. Van Brocklyn JR, Letterle C, Snyder P, Prior T (2002) Sphingosine-1-phosphate stimulates human glioma cell proliferation through Gi-coupled receptors: role of ERK MAP kinase and phosphatidylinositol 3-kinase beta. Cancer Lett 181:195–204

    Article  PubMed  Google Scholar 

  47. Morris AJ, Panchatcharam M, Cheng HY et al (2009) Regulation of blood and vascular cell function by bioactive lysophospholipids. J Thrombosis and Haemostasis 7(Suppl):43

    Google Scholar 

  48. Lee OH, Kim YM, Lee YM et al (1999) Sphingosine 1-phosphate induces angiogenesis: its angiogenic action and signaling mechanism in human umbilical vein endothelial cells. Biochem Biophys Res Commun 264:743–750

    Article  PubMed  CAS  Google Scholar 

  49. Paik JH, Skoura A (2004) Chae SS et al Sphingosine 1-phosphate receptor regulation of N-cadherin mediates vascular stabilization. Genes Dev 18:2392–2403

    Article  PubMed  CAS  Google Scholar 

  50. Chae SS, Paik JH, Furneaux H, Hla T (2004) Requirement for sphingosine 1-phosphate receptor-1 in tumor angiogenesis demonstrated by in vivo RNA interference. J Clin Invest 114:1082–1089

    PubMed  CAS  Google Scholar 

  51. Kono M, Mi Y, Liu Y, Sasaki T et al (2004) The sphingosine-1-phosphate receptors S1P1, S1P2, and S1P3 function coordinately during embryonic angiogenesis. J Biol Chem 279:29367–29373

    Article  PubMed  CAS  Google Scholar 

  52. Brinkmann V (2007) Sphingosine 1-phosphate receptors in health and disease: Mechanistic insights from gene deletion studies and reverse pharmacology. Pharmacol Ther 115:84–105

    Article  PubMed  CAS  Google Scholar 

  53. Mandala S, Hajdu R, Bergstrom J et al (2002) Alteration of lymphocyte trafficking by sphingosine-1-phosphate receptor agonists. Science 296:346–349

    Article  PubMed  CAS  Google Scholar 

  54. LaMontagne K, Littlewood-Evans A, Schnell C et al (2006) Antagonism of sphingosine-1-phosphate receptors by FTY720 inhibits angiogenesis and tumor vascularization. Cancer Res 66:221–231

    Article  PubMed  CAS  Google Scholar 

  55. Theilmeier G, Schmidt C, Herrmann J et al (2006) High-density lipoproteins and their constituent, sphingosine-1-phosphate, directly protect the heart against ischemia/reperfusion injury in vivo via the S1P3 lysophospholipid receptor. Circulation 114:1403–1409

    Article  PubMed  CAS  Google Scholar 

  56. Visentin B, Vekich JA, Sibbald BJ et al (2006) Validation of an anti-sphingosine-1-phosphate antibody as a potential therapeutic in reducing growth, invasion, and angiogenesis in multiple tumor lineages. Cancer Cell 9:225–238

    Article  PubMed  CAS  Google Scholar 

  57. Yamaguchi H, Kitayama J, Takuwa N et al (2003) Sphingosine-1-phosphate receptor subtype-specific positive and negative regulation of Rac and haematogenous metastasis of melanoma cells. Biochem J 374:715–722

    Article  PubMed  CAS  Google Scholar 

  58. Arikawa K, Takuwa N, Yamaguchi H et al (2003) Ligand-dependent inhibition of B16 melanoma cell migration and invasion via endogenous S1P2 G protein-coupled receptor. Requirement of inhibition of cellular RAC activity. J Biol Chem 278:32841–32851

    Article  PubMed  CAS  Google Scholar 

  59. Matloubian M, Lo CG, Cinamon G et al (2004) Lymphocyte egress from thymus and peripheral lymphoid organs is dependent on S1P receptor 1. Nature 427:355–360

    Article  PubMed  CAS  Google Scholar 

  60. Dorsam G, Graeler MH, Seroogy C et al (2003) Transduction of multiple effects of sphingosine 1-phosphate (S1P) on T cell functions by the S1P1 G protein-coupled receptor. J Immunol 171:3500–3507

    PubMed  CAS  Google Scholar 

  61. English D, Kovala AT, Welch Z et al (1999) Induction of endothelial cell chemotaxis by sphingosine 1-phosphate and stabilization of endothelial monolayer barrier function by lysophosphatidic acid, potential mediators of hematopoietic angiogenesis. J Hematother Stem Cell Res 8:627–634

    Article  PubMed  CAS  Google Scholar 

  62. Kveberg L, Bryceson Y, Inngjerdingen M et al (2003) Sphingosine 1 phosphate induces the chemotaxis of human natural killer cells. Role for heterotrimeric G proteins and phosphoinositide 3 kinases. Eur J Immunol 32:1856–1864

    Article  Google Scholar 

  63. Annabi B, Lachambre MP, Plouffe K et al (2009) Modulation of invasive properties of CD133 (+) glioblastoma stem cells: a role for MT1-MMP in bioactive lysophospholipid signaling. Mol Carcinogenesis 48:910–919

    Article  CAS  Google Scholar 

  64. Park KS, Kim MK, Lee HY et al (2007) S1P stimulates chemotactic migration and invasion in OVCAR3 ovarian cancer cells. Biochem Biophys Res Commun 356:239–244

    Article  PubMed  CAS  Google Scholar 

  65. Okamoto H, Takuwa N, Yokomizo T et al (2000) Inhibitory regulation of Rac activation, membrane ruffling, and cell migration by the G protein-coupled sphingosine-1-phosphate receptor EDG5 but not EDG1 or EDG3. Mol Cell Biol 20:9247–9261

    Article  PubMed  CAS  Google Scholar 

  66. Lin DA, Boyce JA (2006) Lysophospholipids as mediators of immunity. Adv Immunol 89:141–167

    Article  PubMed  CAS  Google Scholar 

  67. Tigyi G (2010) Aiming drug discovery at lysophosphatidic acid targets. Br J Pharmacol 161:241–270

    Article  PubMed  CAS  Google Scholar 

  68. Radeff-Huang J, Seasholtz TM, Matteo RG, Brown JH (2004) G protein mediated signaling pathways in lysophospholipid induced cell proliferation and survival. J Cell Biochem 92:949–966

    Article  PubMed  CAS  Google Scholar 

  69. Liu S, Umezu-Goto M, Murph M et al (2009) Expression of autotaxin and lysophosphatidic acid receptors increases mammary tumorigenesis, invasion, and metastases. Cancer Cell 15:539–550

    Article  PubMed  CAS  Google Scholar 

  70. Li H, Wang D, Zhang H, Kirmani K et al (2009) Lysophosphatidic acid stimulates cell migration, invasion, and colony formation as well as tumorigenesis/metastasis of mouse ovarian cancer in immunocompetent mice. Mol Cancer Ther 8:1692–1701

    Article  PubMed  CAS  Google Scholar 

  71. Hu YL, Tee MK, Goetzl EJ et al (2001) Lysophosphatidic acid induction of vascular endothelial growth factor expression in human ovarian cancer cells. J Natl Cancer Inst 93:762–768

    Article  PubMed  CAS  Google Scholar 

  72. Xu X, Prestwich GD (2010) Inhibition of tumor growth and angiogenesis by a lysophosphatidic acid antagonist in an engineered three-dimensional lung cancer xenograft model. Cancer 116:1739–1750

    Article  PubMed  CAS  Google Scholar 

  73. Shin KJ, Kim YL, Lee S, Kim D et al (2009) Lysophosphatidic acid signaling through LPA receptor subtype 1 induces colony scattering of gastrointestinal cancer cells. J Cancer Res Clin Oncol 135:45–52

    Article  PubMed  CAS  Google Scholar 

  74. Zeng Y, Kakehi Y, Nouh MA et al (2009) Gene expression profiles of lysophosphatidic acid-related molecules in the prostate: relevance to prostate cancer and benign hyperplasia. Prostate 69:283–292

    Article  PubMed  CAS  Google Scholar 

  75. Lin S, Wang D, Iyer S, Ghaleb AM et al (2009) The absence of LPA2 attenuates tumor formation in an experimental model of colitis-associated cancer. Gastroenterology 136:1711

    Article  PubMed  CAS  Google Scholar 

  76. Shida D, Kitayama J, Yamaguchi H et al (2003) Lysophosphatidic acid (LPA) enhances the metastatic potential of human colon carcinoma DLD1 cells through LPA1. Cancer Res 63:1706–1711

    PubMed  CAS  Google Scholar 

  77. Fang X, Schummer M, Mao M et al (2002) Lysophosphatidic acid is a bioactive mediator in ovarian cancer. Biochim Biophys Acta 1582:257–264

    PubMed  CAS  Google Scholar 

  78. Goetzl EJ, Dolezalova H, Kong Y et al (1999) Distinctive expression and functions of the type 4 endothelial differentiation gene-encoded G protein-coupled receptor for lysophosphatidic acid in ovarian cancer. Cancer Res 59:5370–5375

    PubMed  CAS  Google Scholar 

  79. Ye X, Hama K, Contos JJ et al (2005) LPA3-mediated lysophosphatidic acid signalling in embryo implantation and spacing. Nature 435:104–108

    Article  PubMed  CAS  Google Scholar 

  80. van Meeteren LA, Ruurs P et al (2006) Autotaxin, a secreted lysophospholipase D, is essential for blood vessel formation during development. Mol Cell Biol 26:5015–5022

    Article  PubMed  CAS  Google Scholar 

  81. Yu S, Murph MM, Lu Y et al (2008) Lysophosphatidic acid receptors determine tumorigenicity and aggressiveness of ovarian cancer cells. J Natl Cancer Inst 100:1630–1642

    Article  PubMed  CAS  Google Scholar 

  82. Jeon ES, Heo SC, Lee IH et al (2010) Ovarian cancer-derived lysophosphatidic acid stimulates secretion of VEGF and stromal cell-derived factor-1 from human mesenchymal stem cells. Exp Mol Med 42:280–293

    Article  PubMed  CAS  Google Scholar 

  83. Ptaszynska MM, Pendrak ML, Stracke ML, Roberts DD (2010) Autotaxin signaling via lysophosphatidic acid receptors contributes to vascular endothelial growth factor-induced endothelial cell migration. Mol Cancer Res 8:309–321

    Article  PubMed  CAS  Google Scholar 

  84. Lin CI, Chen CN, Huang MT et al (2008) Lysophosphatidic acid upregulates vascular endothelial growth factor-C and tube formation in human endothelial cells through LPA(1/3), COX-2, and NF-kappaB activation- and EGFR transactivation-dependent mechanisms. Cell Signal 20:1804–1814

    Article  PubMed  CAS  Google Scholar 

  85. Boucharaba A, Guillet B, Menaa F et al (2009) Bioactive lipids lysophosphatidic acid and sphingosine 1-phosphate mediate breast cancer cell biological functions through distinct mechanisms. Oncol Res 18:173–184

    Article  PubMed  CAS  Google Scholar 

  86. Fang X, Yu S, Bast RC et al (2004) Mechanisms for lysophosphatidic acid-induced cytokine production in ovarian cancer cells. J Biol Chem 279:9653–9661

    Article  PubMed  CAS  Google Scholar 

  87. Wang FQ, Ariztia EV, Boyd LR et al (2010) Lysophosphatidic acid (LPA) effects on endometrial carcinoma in vitro proliferation, invasion, and matrix metalloproteinase activity. Gynecol Oncol 117:88–95

    Article  PubMed  CAS  Google Scholar 

  88. Degousee N, Stefanski E, Lindsay TF et al (2001) p38 MAPK regulates group IIa phospholipase A2 expression in interleukin-1beta -stimulated rat neonatal cardiomyocytes. J Biol Chem 276:43842–43849

    Article  PubMed  CAS  Google Scholar 

  89. Goetzl EJ, Graeler M, Huang MC, Shankar G (2002) Lysophospholipid growth factors and their G protein-coupled receptors in immunity, coronary artery disease, and cancer. ScientificWorldJournal 2:324–338

    Article  PubMed  CAS  Google Scholar 

  90. Stam JC, Michiels F, van der Kammen RA et al (1998) Invasion of T-lymphoma cells: cooperation between Rho family GTPases and lysophospholipid receptor signaling. EMBO J 17:4066–4074

    Article  PubMed  CAS  Google Scholar 

  91. Schwab SR, Cyster JG (2007) Finding a way out: lymphocyte egress from lymphoid organs. Nat Immunol 8:1295–1301

    Article  PubMed  CAS  Google Scholar 

  92. Graeler M, Goetzl EJ (2002) Activation-regulated expression and chemotactic function of sphingosine 1-phosphate receptors in mouse splenic T cells. FASEB J 16:1874–1878

    Article  PubMed  CAS  Google Scholar 

  93. Chi H, Flavell RA (2005) Regulation of T cell trafficking and primary immune responses by sphingosine 1-phosphate receptor 1. J Immunol 174:2485–2488

    PubMed  CAS  Google Scholar 

  94. Morris MA, Gibb DR, Picard F et al (2005) Transient T cell accumulation in lymph nodes and sustained lymphopenia in mice treated with FTY720. Eur J Immunol 35:3570–3580

    Article  PubMed  CAS  Google Scholar 

  95. Rosen H, Sanna MG, Cahalan SM, Gonzalez-Cabrera PJ (2007) Tipping the gatekeeper: S1P regulation of endothelial barrier function. Trends Immunol 28:102–107

    Article  PubMed  CAS  Google Scholar 

  96. Allende ML, Dreier JL, Mandala S, Proia RL (2004) Expression of the sphingosine 1-phosphate receptor, S1P1, on T-cells controls thymic emigration. J Biol Chem 279:15396–15401

    Article  PubMed  CAS  Google Scholar 

  97. Wei SH, Rosen H, Matheu MP et al (2005) Sphingosine 1-phosphate type 1 receptor agonism inhibits transendothelial migration of medullary T cells to lymphatic sinuses. Nat Immunol 6:1228–1235

    Article  PubMed  CAS  Google Scholar 

  98. Sanna MG, Wang SK, Gonzalez-Cabrera PJ et al (2006) Enhancement of capillary leakage and restoration of lymphocyte egress by a chiral S1P1 antagonist in vivo. Nat Chem Biol 2:434–441

    Article  PubMed  CAS  Google Scholar 

  99. Sawicka E, Zuany-Amorim C, Manlius C et al (2003) Inhibition of Th1- and Th2-mediated airway inflammation by the sphingosine 1-phosphate receptor agonist FTY720. J Immunol 171:6206–6214

    PubMed  CAS  Google Scholar 

  100. Jin Y, Knudsen E, Wang L, Bryceson Y et al (2003) Sphingosine 1-phosphate is a novel inhibitor of T-cell proliferation. Blood 101:4909–4915

    Article  PubMed  CAS  Google Scholar 

  101. Wang L, Knudsen E, Jin Y, Gessani S, Maghazachi AA (2004) Lysophospholipids and chemokines activate distinct signal transduction pathways in T helper 1 and T helper 2 cells. Cell Signal 16:991–1000

    PubMed  CAS  Google Scholar 

  102. Wolf AM, Eller K, Zeiser R et al (2009) The sphingosine 1-phosphate agonist FTY720 potently inhibits regulatory T cell proliferation in vitro and in vivo. J Immunol 183:3751–3760

    Article  PubMed  CAS  Google Scholar 

  103. Idzko M, Panther E, Corinti S et al (2002) Sphingosine 1-phosphate induces chemotaxis of immature and modulates cytokine-release in mature human dendritic cells for emergence of Th2 immune responses. FASEB J 16:625–627

    PubMed  CAS  Google Scholar 

  104. Eigenbrod S, Derwand R, Jakl V et al (2006) Sphingosine kinase and sphingosine-1-phosphate regulate migration, endocytosis and apoptosis of dendritic cells. Immunol Invest 35:149–165

    Article  PubMed  CAS  Google Scholar 

  105. Panther E, Idzko M, Corinti S et al (2002) The influence of lysophosphatidic acid on the functions of human dendritic cells. J Immunol 169:4129–4135

    PubMed  CAS  Google Scholar 

  106. Oz-Arslan D, Ruscher W, Myrtek D et al (2006) IL-6 and IL-8 release is mediated via multiple signaling pathways after stimulating dendritic cells with lysophospholipids. J Leukoc Biol 80:287–297

    Article  PubMed  CAS  Google Scholar 

  107. Albertsson PA, Basse PH, Hokland M et al (2003) NK cells and the tumour microenvironment: implications for NK-cell function and anti-tumour activity. Trends Immunol 24:603–609

    Article  PubMed  CAS  Google Scholar 

  108. Maghazachi AA, Al-Aoukaty A (1998) Chemokines activate natural killer cells through heterotrimeric G-proteins: implications for the treatment of AIDS and cancer. FASEB J 12:913–924

    PubMed  CAS  Google Scholar 

  109. Maghazachi AA (2010) Role of chemokines in the biology of natural killer cells. Curr Top Microbiol Immunol 341:37–58

    Article  PubMed  CAS  Google Scholar 

  110. Lagadari M, Lehmann K, Ziemer M et al (2009) Sphingosine-1-phosphate inhibits the cytotoxic activity of NK cells via Gs protein-mediated signalling. Int J Oncol 34:287–294

    PubMed  CAS  Google Scholar 

  111. Rolin J, Sand KL, Knudsen E, Maghazachi AA (2010) FTY720 and SEW2871 reverse the inhibitory effect of S1P on natural killer cell mediated lysis of K562 tumor cells and dendritic cells but not on cytokine release. Cancer Immunol Immunother 59:575–586

    Article  PubMed  CAS  Google Scholar 

  112. Jin Y, Knudsen E, Wang L, Maghazachi AA (2003) Lysophosphatidic acid induces human natural killer cell chemotaxis and intracellular calcium mobilization. Eur J Immunol 33:2083–2089

    Article  PubMed  CAS  Google Scholar 

  113. Lagadari M, Truta-Feles K, Lehmann K et al (2009) Lysophosphatidic acid inhibits the cytotoxic activity of NK cells: involvement of Gs protein-mediated signaling. Int Immunol 21:667–677

    Article  PubMed  CAS  Google Scholar 

  114. Shankaran V, Ikeda H, Bruce AT et al (2001) IFNγ and lymphocytes prevent primary tumour development and shape tumour immunogenicity. Nature 410:1071–111

    Article  Google Scholar 

  115. Sand KL, Knudsen E, Rolin J et al (2009) Modulation of natural killer cell cytotoxicity and cytokine release by the drug glatiramer acetate. Cell Mol Life Sci 66:1446–1456

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The work in the authors’ laboratory is supported by grants from the Norwegian Cancer Society, University of Oslo, UNIFOR, and Forskerlinjen fellowships.

Author information

Authors and Affiliations

  1. Department of Physiology, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, POB 1103 Blindern, 0317, Oslo, Norway

    Johannes Rolin & Azzam A. Maghazachi

Authors
  1. Johannes Rolin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Azzam A. Maghazachi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Johannes Rolin.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rolin, J., Maghazachi, A.A. Effects of Lysophospholipids on Tumor Microenvironment. Cancer Microenvironment 4, 393–403 (2011). https://doi.org/10.1007/s12307-011-0088-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12307-011-0088-1

Keywords

Search

Navigation