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.

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Lysophosphatidylcholine (lysoPC), a product of phosphatidylcholine (PC) hydrolysis via phospholipase A activity, has been proposed to activate cells from a number of lineages. Here, we demonstrate that lysoPC levels are significantly elevated (by 43% overall, relative to normal controls) in the plasma of ovarian cancer patients. This does not appear to be common to all cancers as 5 out of 6 leukemia patients tested had markedly lower (less than one-half of normal) plasma lysoPC. In the plasma of ovarian cancer patients, the percentages of palmitoyl- and stearoyl-lysoPC species were significantly higher, whereas oleoyl and particularly linoleoyl-lysoPC were significantly lower than in control subjects. The molar ratios of lysoPC/PC and palmitoyl-lysoPC/linoleoyl-lysoPC were also significantly elevated in the plasma of ovarian cancer patients compared with those of control subjects. Furthermore, the calculated value of plasma (lysoPC/ PC) x (palmitoyl-lysoPC/linoleoyl-lysoPC) was markedly higher in patients compared with controls.

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