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Lipid Generation and Signaling in Ovarian Cancer

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Ovarian Cancer

Part of the book series: Cancer Treatment and Research ((CTAR,volume 149))

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References

  1. Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2008. CA Cancer J Clin. 2008;58(2):71–96.

    PubMed  Google Scholar 

  2. Bast RC Jr, Brewer M, Zou C, et al. Prevention and early detection of ovarian cancer: mission impossible? Recent Results Cancer Res. 2007;174:91–100.

    CAS  PubMed  Google Scholar 

  3. Berchuck A. Biomarkers in the ovary. J Cell Biochem Suppl. 1995;23:223–226.

    CAS  PubMed  Google Scholar 

  4. Berchuck A, Elbendary A, Havrilesky L, Rodriguez GC, Bast RC Jr. Pathogenesis of ovarian cancers. J Soc Gynecol Investig. 1994;1(3):181–190.

    CAS  PubMed  Google Scholar 

  5. Xu Y, Gaudette DC, Boynton JD, et al. Characterization of an ovarian cancer activating factor in ascites from ovarian cancer patients. Clin Cancer Res. 1995;1(10):1223–1232.

    CAS  PubMed  Google Scholar 

  6. Xu Y, Fang XJ, Casey G, Mills GB. Lysophospholipids activate ovarian and breast cancer cells. Biochem J. 1995;309(Pt 3):933–940.

    CAS  PubMed  Google Scholar 

  7. Umezu-Goto M, Tanyi J, Lahad J, et al. Lysophosphatidic acid production and action: validated targets in cancer? J Cell Biochem. 2004;92(6):1115–1140.

    CAS  PubMed  Google Scholar 

  8. Sutphen R, Xu Y, Wilbanks GD, et al. Lysophospholipids are potential biomarkers of ovarian cancer. Cancer Epidemiol Biomarkers Prev. 2004;13(7):1185–1191.

    CAS  PubMed  Google Scholar 

  9. Xu Y, Xiao YJ, Baudhuin LM, Schwartz BM. The role and clinical applications of bioactive lysolipids in ovarian cancer. J Soc Gynecol Investig. 2001;8(1):1–13.

    PubMed  Google Scholar 

  10. Sengupta S, Wang Z, Tipps R, Xu Y. Biology of LPA in health and disease. Semin Cell Dev Biol. 2004;15(5):503–512.

    CAS  PubMed  Google Scholar 

  11. Fang X, Schummer M, Mao M, et al. Lysophosphatidic acid is a bioactive mediator in ovarian cancer. Biochim Biophys Acta. 2002;1582(1–3):257–264.

    CAS  PubMed  Google Scholar 

  12. Mills GB, Eder A, Fang X, et al. Critical role of lysophospholipids in the pathophysiology, diagnosis, and management of ovarian cancer. Cancer Treat Res. 2002;107:259–283.

    CAS  PubMed  Google Scholar 

  13. Fang X, Gaudette D, Furui T, et al. Lysophospholipid growth factors in the initiation, progression, metastases, and management of ovarian cancer. Ann N Y Acad Sci. 2000;905:188–208.

    CAS  PubMed  Google Scholar 

  14. Mills GB, Moolenaar WH. The emerging role of lysophosphatidic acid in cancer. Nat Rev Cancer. 2003;3(8):582–591.

    CAS  PubMed  Google Scholar 

  15. Xu Y, Sengupta S, Singh S, Steinmetz R. Novel lipid signaling pathways in ovarian cancer cells. Cell Sci Rev. 2006;3:168–197.

    Google Scholar 

  16. Xu Y, Shen Z, Wiper DW, et al. Lysophosphatidic acid as a potential biomarker for ovarian and other gynecologic cancers. JAMA. 1998;280(8):719–723.

    CAS  PubMed  Google Scholar 

  17. Yoon HR, Kim H, Cho SH. Quantitative analysis of acyl-lysophosphatidic acid in plasma using negative ionization tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2003;788(1):85–92.

    CAS  PubMed  Google Scholar 

  18. Sedlakova I, Vavrova J, Tosner J, Hanousek L. Lysophosphatidic acid in ovarian cancer patients. Ceska Gynekol. 2006;71(4):312–317.

    CAS  PubMed  Google Scholar 

  19. Umezu-Goto M, Kishi Y, Taira A, et al. Autotaxin has lysophospholipase D activity leading to tumor cell growth and motility by lysophosphatidic acid production. J Cell Biol. 2002;158(2):227–233.

    CAS  PubMed  Google Scholar 

  20. Tokumura A. Physiological and pathophysiological roles of lysophosphatidic acids produced by secretory lysophospholipase D in body fluids. Biochim Biophys Acta. 2002;1582(1–3):18–25.

    CAS  PubMed  Google Scholar 

  21. Nicosia SV, Bai W, Cheng JQ, Coppola D, Kruk PA. Oncogenic pathways implicated in ovarian epithelial cancer. Hematol Oncol Clin North Am. 2003;17(4):927–943.

    PubMed  Google Scholar 

  22. Kostenis E. Novel clusters of receptors for sphingosine-1-phosphate, sphingosylphosphorylcholine, and (lyso)-phosphatidic acid: new receptors for “old” ligands. J Cell Biochem. 2004;92(5):923–936.

    CAS  PubMed  Google Scholar 

  23. Huang MC, Graeler M, Shankar G, Spencer J, Goetzl EJ. Lysophospholipid mediators of immunity and neoplasia. Biochim Biophys Acta. 2002;1582(1–3):161–167.

    CAS  PubMed  Google Scholar 

  24. Goetzl EJ, Graeler M, Huang MC, Shankar G. Lysophospholipid growth factors and their G protein-coupled receptors in immunity, coronary artery disease, and cancer. Sci World J. 2002;2:324–338.

    CAS  Google Scholar 

  25. Contos JJ, Ishii I, Chun J. Lysophosphatidic acid receptors. Mol Pharmacol. 2000;58(6):1188–1196.

    CAS  PubMed  Google Scholar 

  26. Budnik LT, Mukhopadhyay AK. Lysophosphatidic acid and its role in reproduction. Biol Reprod. 2002;66(4):859–865.

    CAS  PubMed  Google Scholar 

  27. Tigyi G, Parrill AL. Molecular mechanisms of lysophosphatidic acid action. Prog Lipid Res. 2003;42(6):498–526.

    CAS  PubMed  Google Scholar 

  28. Aoki J, Taira A, Takanezawa Y, et al. Serum lysophosphatidic acid is produced through diverse phospholipase pathways. J Biol Chem. 2002;277(50):48737–48744.

    CAS  PubMed  Google Scholar 

  29. Aoki J. Mechanisms of lysophosphatidic acid production. Semin Cell Dev Biol. 2004;15(5):477–489.

    CAS  PubMed  Google Scholar 

  30. Tokumura A, Harada K, Fukuzawa K, Tsukatani H. Involvement of lysophospholipase D in the production of lysophosphatidic acid in rat plasma. Biochim Biophys Acta. 1986;875(1):31–38.

    CAS  PubMed  Google Scholar 

  31. Tokumura A, Fujimoto H, Yoshimoto O, Nishioka Y, Miyake M, Fukuzawa K. Production of lysophosphatidic acid by lysophospholipase D in incubated plasma of spontaneously hypertensive rats and Wistar Kyoto rats. Life Sci. 1999;65(3):245–253.

    CAS  PubMed  Google Scholar 

  32. Imamura F, Horai T, Mukai M, Shinkai K, Sawada M, Akedo H. Induction of in vitro tumor cell invasion of cellular monolayers by lysophosphatidic acid or phospholipase D. Biochem Biophys Res Commun. 1993;193(2):497–503.

    CAS  PubMed  Google Scholar 

  33. Moolenaar WH. Lysophospholipids in the limelight: autotaxin takes center stage. J Cell Biol. 2002;158(2):197–199.

    CAS  PubMed  Google Scholar 

  34. Tokumura A, Majima E, Kariya Y, et al. Identification of human plasma lysophospholipase D, a lysophosphatidic acid-producing enzyme, as autotaxin, a multifunctional phosphodiesterase. J Biol Chem. 2002;277(42):39436–39442.

    CAS  PubMed  Google Scholar 

  35. van Meeteren LA, Moolenaar WH. Regulation and biological activities of the autotaxin-LPA axis. Prog Lipid Res. 2007;46(2):145–160.

    PubMed  Google Scholar 

  36. Ptaszynska MM, Pendrak ML, Bandle RW, Stracke ML, Roberts DD. Positive feedback between vascular endothelial growth factor-A and autotaxin in ovarian cancer cells. Mol Cancer Res. 2008;6(3):352–363.

    CAS  PubMed  Google Scholar 

  37. Cui P, Tomsig JL, McCalmont WF, et al. Synthesis and biological evaluation of phosphonate derivatives as autotaxin (ATX) inhibitors. Bioorg Med Chem Lett. 2007;17(6):1634–1640.

    CAS  PubMed  Google Scholar 

  38. Kishi Y, Okudaira S, Tanaka M, et al. Autotaxin is overexpressed in glioblastoma multiforme and contributes to cell motility of glioblastoma by converting lysophosphatidylcholine to lysophosphatidic acid. J Biol Chem. 2006;281(25):17492–17500.

    CAS  PubMed  Google Scholar 

  39. Kehlen A, Englert N, Seifert A, et al. Expression, regulation and function of autotaxin in thyroid carcinomas. Int J Cancer. 2004;109(6):833–838.

    CAS  PubMed  Google Scholar 

  40. Quinones LG, Garcia-Castro I. Characterization of human melanoma cell lines according to their migratory properties in vitro. In Vitro Cell Dev Biol Anim. 2004;40(1–2):35–42.

    PubMed  Google Scholar 

  41. Desplaces A, Poupon MF. The metastatic process. Bull Cancer. 1994;81(9):751–754.

    CAS  PubMed  Google Scholar 

  42. Stracke ML, Krutzsch HC, Unsworth EJ, et al. Identification, purification, and partial sequence analysis of autotaxin, a novel motility-stimulating protein. J Biol Chem. 1992;267(4):2524–2529.

    CAS  PubMed  Google Scholar 

  43. Tokumura A, Kume T, Fukuzawa K, et al. Peritoneal fluids from patients with certain gynecologic tumor contain elevated levels of bioactive lysophospholipase D activity. Life Sci. 2007;80(18):1641–1649.

    CAS  PubMed  Google Scholar 

  44. Clair T, Aoki J, Koh E, et al. Autotaxin hydrolyzes sphingosylphosphorylcholine to produce the regulator of migration, sphingosine-1-phosphate. Cancer Res. 2003;63(17):5446–5453.

    CAS  PubMed  Google Scholar 

  45. Ren J, Xiao YJ, Singh LS, et al. Lysophosphatidic acid is constitutively produced by human peritoneal mesothelial cells and enhances adhesion, migration, and invasion of ovarian cancer cells. Cancer Res. 2006;66(6):3006–3014.

    CAS  PubMed  Google Scholar 

  46. Hu YL, Tee MK, Goetzl EJ, et al. Lysophosphatidic acid induction of vascular endothelial growth factor expression in human ovarian cancer cells. J Natl Cancer Inst. 2001;93(10):762–768.

    CAS  PubMed  Google Scholar 

  47. Tokumura A, Kanaya Y, Miyake M, Yamano S, Irahara M, Fukuzawa K. Increased production of bioactive lysophosphatidic acid by serum lysophospholipase D in human pregnancy. Biol Reprod. 2002;67(5):1386–1392.

    CAS  PubMed  Google Scholar 

  48. van Meeteren LA, Ruurs P, Christodoulou E, et al. Inhibition of autotaxin by lysophosphatidic acid and sphingosine 1-phosphate. J Biol Chem. 2005;280(22):21155–21161.

    PubMed  Google Scholar 

  49. Clair T, Koh E, Ptaszynska M, et al. L-histidine inhibits production of lysophosphatidic acid by the tumor-associated cytokine, autotaxin. Lipids Health Dis. 2005;4(1):5.

    PubMed  Google Scholar 

  50. Chen M, O'Connor KL. Integrin alpha6beta4 promotes expression of autotaxin/ENPP2 autocrine motility factor in breast carcinoma cells. Oncogene. 2005;24(32):5125–5130.

    CAS  PubMed  Google Scholar 

  51. Baumforth KR, Flavell JR, Reynolds GM, et al. Induction of autotaxin by the Epstein-Barr virus promotes the growth and survival of Hodgkin lymphoma cells. Blood. 2005;106(6):2138–2146.

    CAS  PubMed  Google Scholar 

  52. Harris AL. Hypoxia – a key regulatory factor in tumour growth. Nat Rev Cancer. 2002;2(1):38–47.

    CAS  PubMed  Google Scholar 

  53. Pugh CW, Ratcliffe PJ. Regulation of angiogenesis by hypoxia: role of the HIF system. Nat Med. 2003;9(6):677–684.

    CAS  PubMed  Google Scholar 

  54. Semenza GL. Targeting HIF-1 for cancer therapy. Nat Rev Cancer. 2003;3(10):721–732.

    CAS  PubMed  Google Scholar 

  55. Kim KS, Sengupta S, Berk M, et al. Hypoxia enhances lysophosphatidic acid responsiveness in ovarian cancer cells and lysophosphatidic acid induces ovarian tumor metastasis in vivo. Cancer Res. 2006;66(16):7983–7990.

    CAS  PubMed  Google Scholar 

  56. Xiao Y, Chen Y, Kennedy AW, Belinson J, Xu Y. Evaluation of plasma lysophospholipids for diagnostic significance using electrospray ionization mass spectrometry (ESI-MS) analyses. Ann N Y Acad Sci. 2000;905:242–259.

    CAS  PubMed  Google Scholar 

  57. Xiao YJ, Schwartz B, Washington M, et al. Electrospray ionization mass spectrometry analysis of lysophospholipids in human ascitic fluids: comparison of the lysophospholipid contents in malignant vs. nonmalignant ascitic fluids. Anal Biochem. 2001;290(2):302–313.

    CAS  PubMed  Google Scholar 

  58. le Balle F, Simon MF, Meijer S, Fourcade O, Chap H. Membrane sidedness of biosynthetic pathways involved in the production of lysophosphatidic acid. Adv Enzyme Regul. 1999;39:275–284.

    CAS  PubMed  Google Scholar 

  59. Balsinde J, Balboa MA. Cellular regulation and proposed biological functions of group VIA calcium-independent phospholipase A2 in activated cells. Cell Signal. 2005;17(9):1052–1062.

    CAS  PubMed  Google Scholar 

  60. Balsinde J, Balboa MA, Insel PA, Dennis EA. Regulation and inhibition of phospholipase A2. Annu Rev Pharmacol Toxicol. 1999;39:175–189.

    CAS  PubMed  Google Scholar 

  61. Kudo I, Murakami M. Phospholipase A2 enzymes. Prostaglandins Other Lipid Mediat. 2002;68–69:3–58.

    PubMed  Google Scholar 

  62. Bonventre JV, Huang Z, Taheri MR, et al. Reduced fertility and postischaemic brain injury in mice deficient in cytosolic phospholipase A2. Nature. 1997;390(6660):622–625.

    CAS  PubMed  Google Scholar 

  63. Eder AM, Sasagawa T, Mao M, Aoki J, Mills GB. Constitutive and lysophosphatidic acid (LPA)-induced LPA production: role of phospholipase D and phospholipase A2. Clin Cancer Res. 2000;6(6):2482–2491.

    CAS  PubMed  Google Scholar 

  64. Cummings BS. Phospholipase A2 as targets for anti-cancer drugs. Biochem Pharmacol. 2007;74(7):949–959.

    CAS  PubMed  Google Scholar 

  65. Nakanishi M, Rosenberg DW. Roles of cPLA2alpha and arachidonic acid in cancer. Biochim Biophys Acta. 2006;1761(11):1335–1343.

    CAS  PubMed  Google Scholar 

  66. Sengupta S, Xiao YJ, Xu Y. A novel laminin-induced LPA autocrine loop in the migration of ovarian cancer cells. FASEB J. 2003;17(11):1570–1572.

    CAS  PubMed  Google Scholar 

  67. Manguikian AD, Barbour SE. Cell cycle dependence of group VIA calcium-independent phospholipase A2 activity. J Biol Chem. 2004;279(51):52881–52892.

    CAS  PubMed  Google Scholar 

  68. Roshak AK, Capper EA, Stevenson C, Eichman C, Marshall LA. Human calcium-independent phospholipase A2 mediates lymphocyte proliferation. J Biol Chem. 2000;275(46):35692–35698.

    CAS  PubMed  Google Scholar 

  69. Hazen SL, Gross RW. Human myocardial cytosolic Ca(2+)-independent phospholipase A2 is modulated by ATP. Concordant ATP-induced alterations in enzyme kinetics and mechanism-based inhibition. Biochem J. 1991;280(Pt 3):581–587.

    CAS  PubMed  Google Scholar 

  70. Shen Z, Belinson J, Morton RE, Xu Y, Xu Y. Phorbol 12-myristate 13-acetate stimulates lysophosphatidic acid secretion from ovarian and cervical cancer cells but not from breast or leukemia cells. Gynecol Oncol. 1998;71(3):364–368.

    CAS  PubMed  Google Scholar 

  71. Zhao X, Wang D, Zhao Z, et al. Caspase-3-dependent activation of calcium-independent phospholipase A2 enhances cell migration in non-apoptotic ovarian cancer cells. J Biol Chem. 2006;281(39):29357–29368.

    CAS  PubMed  Google Scholar 

  72. Sengupta S, Kim KS, Berk MP, et al. Lysophosphatidic acid downregulates tissue inhibitor of metalloproteinases, which are negatively involved in lysophosphatidic acid-induced cell invasion. Oncogene. 2007;26(20):2894–2901.

    CAS  PubMed  Google Scholar 

  73. Song Y, Wilkins P, Hu W, et al. Inhibition of calcium-independent phospholipase A2 suppresses proliferation and tumorigenicity of ovarian carcinoma cells. Biochem J. 2007;406(3):427–436.

    CAS  PubMed  Google Scholar 

  74. Larsson Forsell PK, Runarsson G, Ibrahim M, Bjorkholm M, Claesson HE. On the expression of cytosolic calcium-independent phospholipase A2 (88 kDa) in immature and mature myeloid cells and its role in leukotriene synthesis in human granulocytes. FEBS Lett. 1998;434(3):295–299.

    CAS  PubMed  Google Scholar 

  75. Larsson PK, Claesson HE, Kennedy BP. Multiple splice variants of the human calcium-independent phospholipase A2 and their effect on enzyme activity. J Biol Chem. 1998;273(1):207–214.

    CAS  PubMed  Google Scholar 

  76. Atsumi G, Murakami M, Kojima K, Hadano A, Tajima M, Kudo I. Distinct roles of two intracellular phospholipase A2s in fatty acid release in the cell death pathway. Proteolytic fragment of type IVA cytosolic phospholipase A2alpha inhibits stimulus-induced arachidonate release, whereas that of type VI Ca2+-independent phospholipase A2 augments spontaneous fatty acid release. J Biol Chem. 2000;275(24):18248–18258.

    CAS  PubMed  Google Scholar 

  77. Mazurek S, Boschek CB, Eigenbrodt E. The role of phosphometabolites in cell proliferation, energy metabolism, and tumor therapy. J Bioenerg Biomembr. 1997;29(4):315–330.

    CAS  PubMed  Google Scholar 

  78. Bao S, Miller DJ, Ma Z, et al. Male mice that do not express group VIA phospholipase A2 produce spermatozoa with impaired motility and have greatly reduced fertility. J Biol Chem. 2004;279(37):38194–38200.

    CAS  PubMed  Google Scholar 

  79. Burton CA, Patel S, Mundt S, et al. Deficiency in sPLA(2) does not affect HDL levels or atherosclerosis in mice. Biochem Biophys Res Commun. 2002;294(1):88–94.

    CAS  PubMed  Google Scholar 

  80. Luquain C, Singh A, Wang L, Natarajan V, Morris AJ. Role of phospholipase D in agonist-stimulated lysophosphatidic acid synthesis by ovarian cancer cells. J Lipid Res. 2003;44(10):1963–1975.

    CAS  PubMed  Google Scholar 

  81. Tokumura A, Tsutsumi T, Tsukatani H. Transbilayer movement and metabolic fate of ether-linked phosphatidic acid (1-O-Octadecyl-2-acetyl-sn-glycerol 3-phosphate) in guinea pig peritoneal polymorphonuclear leukocytes. J Biol Chem. 1992;267(11):7275–7283.

    CAS  PubMed  Google Scholar 

  82. Kobayashi N, Nishi T, Hirata T, et al. Sphingosine 1-phosphate is released from the cytosol of rat platelets in a carrier-mediated manner. J Lipid Res. 2006;47(3):614–621.

    CAS  PubMed  Google Scholar 

  83. Amano S, Akutsu N, Ogura Y, Nishiyama T. Increase of laminin 5 synthesis in human keratinocytes by acute wound fluid, inflammatory cytokines and growth factors, and lysophospholipids. Br J Dermatol. 2004;151(5):961–970.

    CAS  PubMed  Google Scholar 

  84. Yamada T, Sato K, Komachi M, et al. Lysophosphatidic acid (LPA) in malignant ascites stimulates motility of human pancreatic cancer cells through LPA1. J Biol Chem. 2004;279(8):6595–6605.

    CAS  PubMed  Google Scholar 

  85. Xu J, Lai YJ, Lin WC, Lin FT. TRIP6 enhances lysophosphatidic acid-induced cell migration by interacting with the lysophosphatidic acid 2 receptor. J Biol Chem. 2004;279(11):10459–10468.

    CAS  PubMed  Google Scholar 

  86. Fang X, Yu S, Bast RC, et al. Mechanisms for lysophosphatidic acid-induced cytokine production in ovarian cancer cells. J Biol Chem. 2004;279(10):9653–9661.

    CAS  PubMed  Google Scholar 

  87. Lee Z, Swaby RF, Liang Y, et al. Lysophosphatidic acid is a major regulator of growth-regulated oncogene alpha in ovarian cancer. Cancer Res. 2006;66(5):2740–2748.

    CAS  PubMed  Google Scholar 

  88. Wang P, Wu X, Chen W, Liu J, Wang X. The lysophosphatidic acid (LPA) receptors their expression and significance in epithelial ovarian neoplasms. Gynecol Oncol. 2007;104(3):714–720.

    CAS  PubMed  Google Scholar 

  89. Murph M, Tanaka T, Liu S, Mills GB. Of spiders and crabs: the emergence of lysophospholipids and their metabolic pathways as targets for therapy in cancer. Clin Cancer Res. 2006;12(22):6598–6602.

    CAS  PubMed  Google Scholar 

  90. Valentine WJ, Fujiwara Y, Tsukahara R, Tigyi G. Lysophospholipid signaling: beyond the EDGs. Biochim Biophys Acta. 2008;1780(3):597–605.

    CAS  PubMed  Google Scholar 

  91. Noguchi K, Ishii S, Shimizu T. Identification of p2y9/GPR23 as a novel G protein-coupled receptor for lysophosphatidic acid, structurally distant from the EDG family. J Biol Chem. 2003;278(28):25600–25606.

    CAS  PubMed  Google Scholar 

  92. Yanagida K, Ishii S, Hamano F, Noguchi K, Shimizu T. LPA4/p2y9/GPR23 mediates Rho-dependent morphological changes in a rat neuronal cell line. J Biol Chem. 2007;282(8):5814–5824.

    CAS  PubMed  Google Scholar 

  93. Lee CW, Rivera R, Gardell S, Dubin AE, Chun J. GPR92 as a new G12/13- and Gq-coupled lysophosphatidic acid receptor that increases cAMP, LPA5. J Biol Chem. 2006;281(33):23589–23597.

    CAS  PubMed  Google Scholar 

  94. Kotarsky K, Boketoft A, Bristulf J, et al. Lysophosphatidic acid binds to and activates GPR92, a G protein-coupled receptor highly expressed in gastrointestinal lymphocytes. J Pharmacol Exp Ther. 2006;318(2):619–628.

    CAS  PubMed  Google Scholar 

  95. Pilquil C, Singh I, Zhang QX, et al. Lipid phosphate phosphatase-1 dephosphorylates exogenous lysophosphatidate and thereby attenuates its effects on cell signalling. Prostaglandins Other Lipid Mediat. 2001;64(1–4):83–92.

    CAS  PubMed  Google Scholar 

  96. Brindley DN, English D, Pilquil C, Buri K, Ling ZC. Lipid phosphate phosphatases regulate signal transduction through glycerolipids and sphingolipids. Biochim Biophys Acta. 2002;1582(1–3):33–44.

    CAS  PubMed  Google Scholar 

  97. Sciorra VA, Morris AJ. Roles for lipid phosphate phosphatases in regulation of cellular signaling. Biochim Biophys Acta. 2002;1582(1–3):45–51.

    CAS  PubMed  Google Scholar 

  98. Pyne S, Long JS, Ktistakis NT, Pyne NJ. Lipid phosphate phosphatases and lipid phosphate signalling. Biochem Soc Trans. 2005;33(Pt 6):1370–1374.

    CAS  PubMed  Google Scholar 

  99. McDermott MI, Sigal YJ, Crump JS, Morris AJ. Enzymatic analysis of lipid phosphate phosphatases. Methods. 2006;39(2):169–179.

    CAS  PubMed  Google Scholar 

  100. Tanyi JL, Hasegawa Y, Lapushin R, et al. Role of decreased levels of lipid phosphate phosphatase-1 in accumulation of lysophosphatidic acid in ovarian cancer. Clin Cancer Res. 2003;9(10 Pt 1):3534–3545.

    CAS  PubMed  Google Scholar 

  101. Tanyi JL, Morris AJ, Wolf JK, et al. The human lipid phosphate phosphatase-3 decreases the growth, survival, and tumorigenesis of ovarian cancer cells: validation of the lysophosphatidic acid signaling cascade as a target for therapy in ovarian cancer. Cancer Res. 2003;63(5):1073–1082.

    CAS  PubMed  Google Scholar 

  102. Imai A, Furui T, Tamaya T, Mills GB. A gonadotropin-releasing hormone-responsive phosphatase hydrolyses lysophosphatidic acid within the plasma membrane of ovarian cancer cells. J Clin Endocrinol Metab. 2000;85(9):3370–3375.

    CAS  PubMed  Google Scholar 

  103. Xie Y, Gibbs TC, Mukhin YV, Meier KE. Role for 18:1 lysophosphatidic acid as an autocrine mediator in prostate cancer cells. J Biol Chem. 2002;277(36):32516–32526.

    CAS  PubMed  Google Scholar 

  104. Tanaka M, Kishi Y, Takanezawa Y, Kakehi Y, Aoki J, Arai H. Prostatic acid phosphatase degrades lysophosphatidic acid in seminal plasma. FEBS Lett. 2004;571(1–3):197–204.

    CAS  PubMed  Google Scholar 

  105. Thompson FJ, Clark MA. Purification of a lysophosphatidic acid-hydrolysing lysophospholipase from rat brain. Biochem J. 1994;300(Pt 2):457–461.

    CAS  PubMed  Google Scholar 

  106. West J, Tompkins CK, Balantac N, et al. Cloning and expression of two human lysophosphatidic acid acyltransferase cDNAs that enhance cytokine-induced signaling responses in cells. DNA Cell Biol. 1997;16(6):691–701.

    CAS  PubMed  Google Scholar 

  107. Springett GM, Bonham L, Hummer A, et al. Lysophosphatidic acid acyltransferase-beta is a prognostic marker and therapeutic target in gynecologic malignancies. Cancer Res. 2005;65(20):9415–9425.

    CAS  PubMed  Google Scholar 

  108. Panetti TS. Differential effects of sphingosine 1-phosphate and lysophosphatidic acid on endothelial cells. Biochim Biophys Acta. 2002;1582(1–3):190–196.

    CAS  PubMed  Google Scholar 

  109. Pyne S, Pyne N. Sphingosine 1-phosphate signalling via the endothelial differentiation gene family of G-protein-coupled receptors. Pharmacol Ther. 2000;88(2):115–131.

    CAS  PubMed  Google Scholar 

  110. Spiegel S, Milstien S. Sphingosine-1-phosphate: signaling inside and out. FEBS Lett. 2000;476(1–2):55–57.

    CAS  PubMed  Google Scholar 

  111. Wymann MP, Schneiter R. Lipid signalling in disease. Nat Rev Mol Cell Biol. 2008;9(2):162–176.

    CAS  PubMed  Google Scholar 

  112. Spiegel S, Kolesnick R. Sphingosine 1-phosphate as a therapeutic agent. Leukemia. 2002;16(9):1596–1602.

    CAS  PubMed  Google Scholar 

  113. Yatomi Y. Plasma sphingosine 1-phosphate metabolism and analysis. Biochim Biophys Acta. 2008;1780(3):606–611.

    CAS  PubMed  Google Scholar 

  114. Hernandez M, Nieto ML, Sanchez Crespo M. Cytosolic phospholipase A2 and the distinct transcriptional programs of astrocytoma cells. Trends Neurosci. 2000;23(6):259–264.

    CAS  PubMed  Google Scholar 

  115. Spiegel S, Milstien S. Exogenous and intracellularly generated sphingosine 1-phosphate can regulate cellular processes by divergent pathways. Biochem Soc Trans. 2003;31(Pt 6):1216–1219.

    CAS  PubMed  Google Scholar 

  116. Spiegel S, Milstien S. Sphingosine-1-phosphate: an enigmatic signalling lipid. Nat Rev Mol Cell Biol. 2003;4(5):397–407.

    CAS  PubMed  Google Scholar 

  117. Yokoo E, Yatomi Y, Takafuta T, Osada M, Okamoto Y, Ozaki Y. Sphingosine 1-phosphate inhibits migration of RBL-2H3 cells via S1P2: cross-talk between platelets and mast cells. J Biochem. 2004;135(6):673–681.

    CAS  PubMed  Google Scholar 

  118. Sugimoto N, Takuwa N, Okamoto H, Sakurada S, Takuwa Y. Inhibitory and stimulatory regulation of Rac and cell motility by the G12/13-Rho and Gi pathways integrated downstream of a single G protein-coupled sphingosine-1-phosphate receptor isoform. Mol Cell Biol. 2003;23(5):1534–1545.

    CAS  PubMed  Google Scholar 

  119. Okamoto H, Takuwa N, Yokomizo T, et al. 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. 2000;20(24):9247–9261.

    CAS  PubMed  Google Scholar 

  120. Yamaguchi H, Kitayama J, Takuwa N, et al. Sphingosine-1-phosphate receptor subtype-specific positive and negative regulation of Rac and haematogenous metastasis of melanoma cells. Biochem J. 2003;374(Pt 3):715–722.

    CAS  PubMed  Google Scholar 

  121. Lee MJ, Thangada S, Paik JH, et al. Akt-mediated phosphorylation of the G protein-coupled receptor EDG-1 is required for endothelial cell chemotaxis. Mol Cell. 2001;8(3):693–704.

    CAS  PubMed  Google Scholar 

  122. Becciolini L, Meacci E, Donati C, Cencetti F, Rapizzi E, Bruni P. Sphingosine 1-phosphate inhibits cell migration in C2C12 myoblasts. Biochim Biophys Acta. 2006;1761(1):43–51.

    CAS  PubMed  Google Scholar 

  123. Pyne S, Pyne NJ. Sphingosine 1-phosphate signalling and termination at lipid phosphate receptors. Biochim Biophys Acta. 2002;1582(1–3):121–131.

    CAS  PubMed  Google Scholar 

  124. Le Stunff H, Peterson C, Liu H, Milstien S, Spiegel S. Sphingosine-1-phosphate and lipid phosphohydrolases. Biochim Biophys Acta. 2002;1582(1–3):8–17.

    CAS  PubMed  Google Scholar 

  125. Brindley DN. Lipid phosphate phosphatases and related proteins: signaling functions in development, cell division, and cancer. J Cell Biochem. 2004;92(5):900–912.

    CAS  PubMed  Google Scholar 

  126. Liu H, Chakravarty D, Maceyka M, Milstien S, Spiegel S. Sphingosine kinases: a novel family of lipid kinases. Prog Nucleic Acid Res Mol Biol. 2002;71:493–511.

    CAS  PubMed  Google Scholar 

  127. Spiegel S, English D, Milstien S. Sphingosine 1-phosphate signaling: providing cells with a sense of direction. Trends Cell Biol. 2002;12(5):236–242.

    CAS  PubMed  Google Scholar 

  128. Mandala SM. Sphingosine-1-phosphate phosphatases. Prostaglandins. 2001;64(1–4):143–156.

    CAS  PubMed  Google Scholar 

  129. Olivera A, Spiegel S. Sphingosine kinase: a mediator of vital cellular functions. Prostaglandins Other Lipid Mediat. 2001;64(1–4):123–134.

    CAS  PubMed  Google Scholar 

  130. Smicun Y, Reierstad S, Wang FQ, Lee C, Fishman DA. S1P regulation of ovarian carcinoma invasiveness. Gynecol Oncol. 2006;103(3):952–959.

    CAS  PubMed  Google Scholar 

  131. Smicun Y, Gil O, Devine K, Fishman DA. S1P and LPA have an attachment-dependent regulatory effect on invasion of epithelial ovarian cancer cells. Gynecol Oncol. 2007;107(2):298–309.

    CAS  PubMed  Google Scholar 

  132. Park KS, Kim MK, Lee HY, et al. S1P stimulates chemotactic migration and invasion in OVCAR3 ovarian cancer cells. Biochem Biophys Res Commun. 2007;356(1):239–244.

    CAS  PubMed  Google Scholar 

  133. Visentin B, Vekich JA, Sibbald BJ, et al. Validation of an anti-sphingosine-1-phosphate antibody as a potential therapeutic in reducing growth, invasion, and angiogenesis in multiple tumor lineages. Cancer Cell. 2006;9(3):225–238.

    CAS  PubMed  Google Scholar 

  134. Murph M, Mills GB. Targeting the lipids LPA and S1P and their signalling pathways to inhibit tumour progression. Expert Rev Mol Med. 2007;9(28):1–18.

    PubMed  Google Scholar 

  135. Singh IN, Hall ED. Multifaceted roles of sphingosine-1-phosphate: how does this bioactive sphingolipid fit with acute neurological injury? J Neurosci Res. 2008; May15;86(7):1419–33.

    Google Scholar 

  136. Merrill AH Jr, Schmelz EM, Dillehay DL, et al. Sphingolipids – the enigmatic lipid class: biochemistry, physiology, and pathophysiology. Toxicol Appl Pharmacol. 1997;142(1):208–225.

    CAS  PubMed  Google Scholar 

  137. Hong G, Baudhuin LM, Xu Y. Sphingosine-1-phosphate modulates growth and adhesion of ovarian cancer cells. FEBS Lett. 1999;460(3):513–518.

    CAS  PubMed  Google Scholar 

  138. Wang FQ, Smicun Y, Calluzzo N, Fishman DA. Inhibition of matrilysin expression by antisense or RNA interference decreases lysophosphatidic acid-induced epithelial ovarian cancer invasion. Mol Cancer Res. 2006;4(11):831–841.

    CAS  PubMed  Google Scholar 

  139. Wang D, Zhao Z, Caperell-Grant A, et al. S1P differentially regulates migration of human ovarian cancer and human ovarian surface epithelial cells. Mol Cancer Ther. 2008 July;7(7):1993–2002.

    Google Scholar 

  140. Takuwa Y, Takuwa N, Sugimoto N. The EDG family G protein-coupled receptors for lysophospholipids: their signaling properties and biological activities. J Biochem (Tokyo). 2002;131(6):767–771.

    CAS  Google Scholar 

  141. Takuwa Y, Okamoto H, Takuwa N, Gonda K, Sugimoto N, Sakurada S. Subtype-specific, differential activities of the EDG family receptors for sphingosine-1-phosphate, a novel lysophospholipid mediator. Mol Cell Endocrinol. 2001;177(1–2):3–11.

    CAS  PubMed  Google Scholar 

  142. Larsson C. Protein kinase C and the regulation of the actin cytoskeleton. Cell Signal. 2006;18(3):276–284.

    CAS  PubMed  Google Scholar 

  143. Adams JC. Cell-matrix contact structures. Cell Mol Life Sci. 2001;58(3):371–392.

    CAS  PubMed  Google Scholar 

  144. Pawlak G, Helfman DM. Cytoskeletal changes in cell transformation and tumorigenesis. Curr Opin Genet Dev. 2001;11(1):41–47.

    CAS  PubMed  Google Scholar 

  145. Pawlak G, Helfman DM. Post-transcriptional down-regulation of ROCKI/Rho-kinase through an MEK-dependent pathway leads to cytoskeleton disruption in Ras-transformed fibroblasts. Mol Biol Cell. 2002;13(1):336–347.

    CAS  PubMed  Google Scholar 

  146. Alemany R, van Koppen CJ, Danneberg K, Ter Braak M, Meyer Zu Heringdorf D. Regulation and functional roles of sphingosine kinases. Naunyn Schmiedebergs Arch Pharmacol. 2007;374(5–6):413–428.

    CAS  PubMed  Google Scholar 

  147. Spiegel S, Milstien S. Sphingosine 1-phosphate, a key cell signaling molecule. J Biol Chem. 2002;277(29):25851–25854.

    CAS  PubMed  Google Scholar 

  148. Moran JM, Buller RM, McHowat J, et al. Genetic and pharmacologic evidence that calcium-independent phospholipase A2beta regulates virus-induced inducible nitric-oxide synthase expression by macrophages. J Biol Chem. 2005;280(30):28162–28168.

    CAS  PubMed  Google Scholar 

  149. Meyer AM, Dwyer-Nield LD, Hurteau GJ, et al. Decreased lung tumorigenesis in mice genetically deficient in cytosolic phospholipase A2. Carcinogenesis. 2004;25(8):1517–1524.

    CAS  PubMed  Google Scholar 

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Acknowledgements

We would like to acknowledge Dr. Paul Fox (The Cleveland Clinic Foundation) for letting us use his hypoxia chamber. This work was supported by NIH grants RO1 CA095042 and CA-89228 (to Y.X.).

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Indiana University, 975 W. Walnut St., IB355A, 46202, Indianapolis, IN, USA

    Yan Xu & Dongmei Wang

  2. Department of Cancer Biology, The Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, 44195, Cleveland, OH, USA

    Zeneng Wang

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  1. Yan Xu
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  2. Dongmei Wang
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  3. Zeneng Wang
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Correspondence to Yan Xu .

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Editors and Affiliations

  1. School of Medicine, University of Missouri, Hospital Dr. 1, Columbia, 65212, U.S.A.

    M. Sharon Stack

  2. School of Medicine, New York University, First Ave. 550, New York, 10016, U.S.A.

    David A. Fishman

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Xu, Y., Wang, D., Wang, Z. (2009). Lipid Generation and Signaling in Ovarian Cancer. In: Stack, M., Fishman, D. (eds) Ovarian Cancer. Cancer Treatment and Research, vol 149. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-98094-2_12

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