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

Zhongzhou Shen, Jerome Belinson, Richard E. Morton, Yan Xu, Yan Xu

Research output: Contribution to journalArticle

98 Citations (Scopus)

Abstract

Lysophosphatidic acid (LPA) is present in ascites from patients with ovarian cancer. It stimulates calcium release and growth of ovarian cancer cells both in vitro and in vivo. Recently, we found that LPA levels were significantly elevated in plasma from patients with ovarian cancer and other gynecological cancers. In contrast, LPA levels were not elevated in patients with breast cancer and leukemias. In view of this, we investigated whether gynecological cancer cells could produce LPA. LPA was extracted from the supernatant of cells cultured in vitro and purified by thin layer chromatography. After hydrolysis and transmethylation, the fatty acid derivatives were analyzed by gas chromatography. We found that the phorbol ester, phorbol 12-myristate 13-acetate (PMA), significantly stimulated the production of LPA in ovarian and cervical cancer cells. In contrast, a small or negligible amount of LPA was produced in breast cancer and leukemia cells upon PMA stimulation. 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 cytosolic PLA2 (cPLA2)/Ca2+ independent PLA2 (iPLA2) inhibitor, AACOCF3, inhibited 75.6% PMA-stimulated LPA secretion in ovarian cancer cells, suggesting a cPLA2/iPLA2 activity was involved in LPA production from ovarian cancer cells.

Original languageEnglish (US)
Pages (from-to)364-368
Number of pages5
JournalGynecologic Oncology
Volume71
Issue number3
DOIs
StatePublished - Dec 1998
Externally publishedYes

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Uterine Cervical Neoplasms
Ovarian Neoplasms
Leukemia
Acetates
Breast
Neoplasms
phorbol-12-myristate
lysophosphatidic acid
Breast Neoplasms
Phorbol Esters
Thin Layer Chromatography
Ascites
Gas Chromatography
Cultured Cells
Hydrolysis
Fatty Acids
Calcium

Keywords

  • LPA production
  • Ovarian cancer cells
  • PKC
  • PLA
  • PMA

ASJC Scopus subject areas

  • Obstetrics and Gynecology
  • Oncology

Cite this

Phorbol 12-myristate 13-acetate stimulates lysophosphatidic acid secretion from ovarian and cervical cancer cells but not from breast or leukemia cells. / Shen, Zhongzhou; Belinson, Jerome; Morton, Richard E.; Xu, Yan; Xu, Yan.

In: Gynecologic Oncology, Vol. 71, No. 3, 12.1998, p. 364-368.

Research output: Contribution to journalArticle

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