Lysophospholipid growth factors in the initiation, progression, metastases, and management of ovarian cancer

Xianjun Fang, Douglas Gaudette, Tatsuro Furui, Muling Mao, Veronica Estrella, Astrid Eder, Terri Pustilnik, Takayo Sasagawa, Ruthie Lapushin, Shiangxing Yu, Robert B. Jaffe, Jon R. Wiener, James R. Erickson, Gordon Mills

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197 Scopus citations

Abstract

Levels of lysophosphatidic acid (LPA) and lysophosphatidylcholine (LPC) are elevated in the plasma and ascites of ovarian cancer patients, but not in most other tumor types. LPA increases cell proliferation, cell survival, resistance to cisplatin, cell shrinkage, and production of vascular endothelial growth factor, urokinase plasminogen activator, and LPA itself in ovarian cancer cells, but not in normal ovarian surface epithelial cells. PSP24 and members of the endothelial differentiation gene (EDG) family (EDG1, EDG2, EDG4, and EDG7) of G protein-coupled receptors mediate LPA signaling. Ovarian cancer cell lines do not express EDG1 mRNA, have variable EDG2 mRNA and protein levels, and frequently exhibit elevated levels of EDG4 mRNA and protein, suggesting that EDG4 may contribute to the deleterious effects of LPA in ovarian cancer. In contrast, activation of the EDG2 LPA receptor on ovarian cancer cells may lead to apoptosis and counter the effects of other LPA receptors. Thus, the development of agonists and antagonists for the appropriate spectrum of LPA receptors may alter proliferation, apoptosis, or response to therapy of ovarian cancer cells. Indeed, over 60% of all current drugs target the G protein-coupled family of receptors, making the LPA receptor family a 'drugable' target. LPC, although not as thoroughly studied, increases cellular proliferation and mediates multiple other functions through unique signaling pathways.

Original languageEnglish (US)
Pages (from-to)188-208
Number of pages21
JournalAnnals of the New York Academy of Sciences
Volume905
Publication statusPublished - May 23 2000
Externally publishedYes

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science

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