Activation of human ovarian cancer cells: role of lipid factors in ascitic fluid

  • Y. Xu
  • G. B. Mills


Normal cells proliferate in response to injury or to replace cells with a limited survival time. This is true for cells in the hematopoietic system and epithelial cells of the skin and bowel. It has been estimated that 1 million cell divisions per second are required for the replacement of lost cells. The proliferation of normal cells is regulated by the action of a number of polypeptide and lipid factors called growth factors [1–8]. These growth factors bind to specific cell surface receptors and transmit activation signals across the cell membrane. These signals initiate a limited number of intracellular biochemical cascades which in turn communicate with the nucleus, eventually leading to cellular proliferation [5–8]. In addition to positive growth signals, a series of proteins is involved in limiting cellular proliferation [9–10]. Several of these, such as p53 and the product of the retinoblastoma gene (RB), are more commonly known as tumor suppressor genes [9,10]. Finally, some activated cells are sensitized to a physiological process Known as programmed cell death or apoptosis [11–13]. Both the products of tumor suppressor genes and the products of the genes involved in programmed cell death must be overcome for a cell to divide.


Ovarian Cancer Ovarian Cancer Cell Ascitic Fluid Ovarian Cancer Patient Lipid Mediator 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    Rozengurt, E. (1992) Growth factors and cell proliferation. Curr. Opin. Cell Biol., 4,161–5.PubMedCrossRefGoogle Scholar
  2. 2.
    Bishop, M. (1991) Molecular themes in oncogenesis. Cell, 64,235–48.PubMedCrossRefGoogle Scholar
  3. 3.
    Aaronson, S.A. (1991) Growth factors and cancer. Science, 254,1146–53.PubMedCrossRefGoogle Scholar
  4. 4.
    Cross, M. and Dexter, T.M. (1991) Growth factors in development, transformation, and tumorigenesis. Cell, 64, 271–80.PubMedCrossRefGoogle Scholar
  5. 5.
    Boyle, W.J. (1992) Growth factors and tyrosine kinase receptors during development and cancer. Curr. Opin. Oncol., 4, 156–62.PubMedCrossRefGoogle Scholar
  6. 6.
    Ullrich, A. and Schlessinger, J. (1990) Signal transduction by receptors with tyrosine kinase activity. Cell, 61,203–12.PubMedCrossRefGoogle Scholar
  7. 7.
    Berridge, M.J. (1993) Inositol triphosphate and calcium signaling. Nature, 361,315–25.PubMedCrossRefGoogle Scholar
  8. 8.
    Schmandt, R. and Mills, G.B. (1993) Genomic components of carcinogenesis. Clin, Chem., 39, 2375–85.Google Scholar
  9. 9.
    Marshall, C.J. (1991) Tumor suppressor genes. Cell, 64,313–26.PubMedCrossRefGoogle Scholar
  10. 10.
    Weinberg, R.A. (1991) Tumor suppressor genes. Science, 254,1138–46.PubMedCrossRefGoogle Scholar
  11. 11.
    Hockenberry, D.M., Nunez, G., Milliman, C. et al., (1990) Bcl-2 is an inner mitochondrial membrane protein that blocks programmed cell death. Nature, 348,334–6.CrossRefGoogle Scholar
  12. 12.
    Grivell, L.A and Jacobs, H.T. (1992) Oncogenes, mitochondria and immortality. Curr. Opin. Immunol, 1,94–6.Google Scholar
  13. 13.
    Williams, G.T. (1991) Programmed cell death: apoptosis and oncogenesis.Cell, 65, 1097–8.PubMedCrossRefGoogle Scholar
  14. 14.
    Mills, G.B., Hashimoto, S., Hurteau, J. et al, (1992) Regulation of growth of human ovarian cancer cells. In Ovarian Cancer 2: Biology, Diagnosis and Management, (eds. F. Sharp Mason and W. Creaseman), Chapman & Hall, London, pp. 127–43.Google Scholar
  15. 15.
    Bast, R.C. Jr., Jacobs, I. and Berchuck, J.A. (1992) Malignant transformation of ovarian epithelium, J. Natl Cancer Inst., 84, 556–8.CrossRefGoogle Scholar
  16. 16.
    Godwin, A.K., Testa, J.R., Handel, L.M. et al., (1992) Spontaneous transformation of rat ovarian surface epithelial cells: association with cytogenetic changes and implications of repeated ovulation in the etiology of ovarian cancer. J. Natl. Cancer Inst., 84, 592–601.PubMedCrossRefGoogle Scholar
  17. 17.
    Mills, G.B., Hashimoto, S., Hurteau, J.A. et al., (1992) Role of growth factors, their receptors, and signaling pathways in the diagnosis, prognosis, follow-up and therapy of ovarian cancer. Diagn. Oncol., 2,39–54.Google Scholar
  18. 18.
    Mills, G.B., May, C., McGill, M. et al., (1988) A putative new growth factor in ascitic fluid from ovarian cancer patients: identification, characterization and mechanism of action. Cancer Res., 48,1066–71.PubMedGoogle Scholar
  19. 19.
    Mills, G.B. and May C. (1989) Regulatory mechanisms in ascitic fluid. In Ovarian Cancer: Biologic and Therapeutic Challenges, (eds. F. Sharp, W.P. Mason and R.E. Leake), Chapman & Hall, London, pp. 55–62.Google Scholar
  20. Hurteau, J., Simon, H.U., Kurman, C. et al, (1993) Levels of the soluble interleukin 2 receptor alpha are elevated in epithelial ovarian cancer patients: evidence for activation of T lymphocytes and potential role in management of ovarian cancer. Am. J. Obstet. Gynecol., in press.Google Scholar
  21. 21.
    Mills, G.B., May, C., Hill, M. et al, (1990) Ascitic fluid from human ovarian cancer patients contains growth factors necessary for intraperitoneal growth of human ovarian cancer cells, J. Clin. Invest., 86,851–5.CrossRefGoogle Scholar
  22. 22.
    Roifman, C.M., Chin, K., Gazit, A. et al, (1991) Tyrosine phosphorylation is an essential event in the stimulation of B lymphocytes by Staphylococcus aureus, Cowan I. J. Immunol, 146,2965–71.PubMedGoogle Scholar
  23. 23.
    Padeh, S., Levitzki, A., Mills, G.B. and Roifman, C.H. (1991) Activation of phospholipase C in human B cells is dependent on tyrosine phosphorylation. J. Clin. Invest., 87, 1114–18.PubMedCrossRefGoogle Scholar
  24. 24.
    Vu, T.K., Hung, D.T., Wheaton, V.l. and Coughlin, S.R. (1991) Molecular cloning of a functional thrombin receptor reveals a novel proteolytic mechanism of receptor activation. Cell, 64,1057–64.PubMedCrossRefGoogle Scholar
  25. 25.
    Needelman, P., Turk, J., Jakschik, B.A. et al., (1983) Arachidonic acid metabolism. Ann. Rev. Biochem., 55, 69–102.CrossRefGoogle Scholar
  26. 26.
    Hanahan, D.J. (1986) Platelet activating factor: a biologically active phosphoglyceride. Ann. Rev. Biochem., 55,438–509.CrossRefGoogle Scholar
  27. 27.
    Lenzen, S., GorHch, J.K. and Rustenbeck, I. (1989) Regulation of transmembrane ion transport by reaction products of phospholipase A2. I. Effects of lysophospholipids on mitochondrial Ca2+ transport. Biochim. Biophys. Acta, 982,140–6.PubMedCrossRefGoogle Scholar
  28. 28.
    Metz, S.A. (1988) Mobilization of cellular Ca2+ by lysophospholipids in rat islets of Langerhans. Biochim. Biophys. Acta, 968, 239–52.PubMedCrossRefGoogle Scholar
  29. 29.
    Bellini, F., Viola, G., Menegus, A.M. et al, (1990) Signalling mechanism in the lysophosphatidylserine-induced activation of mouse mast cells. Biochem. Biophys. Acta, 1052, 216–20.PubMedCrossRefGoogle Scholar
  30. 30.
    Hannun, Y.A., and Bell, R.M. (1989) Functions of sphingolipids and sphingolipid breakdown products in cellular regulation. Science, 243, 500–6.PubMedCrossRefGoogle Scholar
  31. 31.
    Zhang, H., Desai, N.N., Olivera, A. et al, (1991) Sphingosine-l-phosphate, a novel lipid, involved in cellular proliferation, J. Cell Biol., 114,155–67.PubMedCrossRefGoogle Scholar
  32. 32.
    Van Corven, E.J., Groenink, A., Jalink, K. et al, (1989) Lysophosphatidate-induced cell proliferation: identification and dissection of signalling pathways mediated by G proteins. Cell, 59,45–54.PubMedCrossRefGoogle Scholar
  33. 33.
    Honda, Z.I., Nakamura, M., Miki, I. et al, (1991) Cloning by functional expression of platelet-activating factor receptor from guineapig lung. Nature, 349, 342–6.PubMedCrossRefGoogle Scholar
  34. 34.
    Ye, R.D., Prossnitz, E.R., Zou, A. and Cochrane, C.G. (1991) Characterization of a human cDNA that encodes a functional receptor for platelet activating factor. Biochem. Biophy. Res. Comm., 180, 105–11.CrossRefGoogle Scholar
  35. 35.
    Jalink, K., van Corven, E.J. and Moolenaar, W.H. (1990) Lysophosphatidic acid, but not phosphatidic acid, is a potent Ca2+-mobilizing stimulus for fibroblasts.J. Biol Chem., 265, 12232–9.PubMedGoogle Scholar
  36. 36.
    Van Corven, E.J., van Rijswijk, A., Jalink, K. et al, (1992) Mitogenic action of lysophosphatidic acid and phosphatidic acid on fibroblasts. Biochem. J., 281,163–9.PubMedGoogle Scholar
  37. 37.
    Bligh, E.G. and Dyer, W.J. (1959) A rapid method of total lipid extraction and purification. Can. Biochem. Physiol, 37,911–17.CrossRefGoogle Scholar
  38. 38.
    Kates, M. (1978) Techniques of Lipidology, 2nd edn. Elsevier, Amsterdam.Google Scholar
  39. 39.
    Bittman, R., Byun, H.S., Mercier, B. and Salari, H. (1993) 2’-(Trimethylammonio)ethyl-4-(hexadecyloxy)-3(S)-methoxybutane-phosphate: a novel potent antineoplastic agent. J. Med. Chem., 36,297–9.PubMedCrossRefGoogle Scholar

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© Chapman & Hall 1995

Authors and Affiliations

  • Y. Xu
  • G. B. Mills

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