Phorbol 12-myristate 13-acetate stimulates lysophosphatidic acid secretionfrom ovarian and cervical cancer cells but not from breast or leukemia cells

Lysophosphatidic acid (LPA) is present in ascites from patients with ovaria n cancer. It stimulates calcium release and growth of ovarian cancer cells both in vitro and in vivo. Recently, we found that LPA levels were signific antly elevated in plasma from patients with ovarian cancer and other gyneco logical cancers. In contrast, LPA levels were not elevated in patients with breast cancer and leukemias. In view of this, we investigated whether gyne cological cancer cells could produce LPA, LPA was extracted from the supern atant of cells cultured in vitro and purified by thin layer chromatography. After hydrolysis and transmethylation, the fatty acid derivatives were ana lyzed by gas chromatography. We found that the phorbol ester, phorbol 12-my ristate 13-acetate (PMA), significantly stimulated the production of LPA in ovarian and cervical cancer cells. In contrast, a small or negligible amou nt of LPA was produced in breast cancer and leukemia cells upon PMA stimula tion. This cell type specificity correlates with our values of plasma LPA, suggesting that gynecological tumor cells may be an important source of the elevated LPA noted in the plasma of patients with these cancers. The cytos olic PLA, (cPLA(2))/Ca2+-independent PLA(2) (iPLA(2)) inhibitor, AACOCF(3), inhibited 75.6% PMA-stimulated LPA secretion in ovarian cancer cells, sugg esting a cPLA(2)/iPLA(2) activity was involved in LPA production from ovari an cancer cells, (C) 1998 Academic Press.