Characterization of an Ovarian Cancer Activating Factor in Ascites From Ovarian Cancer Patients

Yan Xu, John D. Boynton, Andrea Frankel, Xian Jun Fang, Ajay Sharma, Jean Hurteau, Gordon B. Mills, Anne Goodbody, Graham Casey, Douglas C. Gaudett, Bruce J. Holub, Alan Mellors

Research output: Contribution to journalArticlepeer-review

289 Scopus citations

Abstract

Ascites from ovarian cancer patients contain potent growth-promoting activity toward human ovarian cancer cells both in vitro and in vivo. This activity is associated with rapid increases in cytosolic free calcium ([Ca2+]i) as a consequence of phosphoinositide hydrolysis. In this study, we describe the purification, characterization, and identification of an ovarian cancer activating factor (OCAF) from ascites of ovarian cancer patients. We have isolated OCAF by a combination of solvent extraction, silica gel chromatography, and TLC. Mass spectral analysis, phospholipase sensitivity, and gas chromatographic behavior of purified OCAF indicate that OCAF is composed of various species of lysophosphatidic acid (LPA), including LPAs with polyunsaturated fatty acyl chains (linoleic, arachidonic, and docosahexaenoic acids). However, OCAF is more potent than sn-1 palmitoyl, oleoyl, or stearoyl LPA in increasing [Ca2+]i in ovarian cancer cells. The ability of OCAF to alter [Ca2+]i is sensitive to the effects of lipoxidase, whereas the activity of sn-1 oleoyl, stearoyl, or palmitoyl LPA is not, suggesting that polyunsaturated bonds in the fatty acyl chain of OCAF may account for its increased ability to activate ovarian cancer cells. Furthermore, a sn-2 linoleoyl LPA generated by phospholipase A, treatment of synthetic phosphatidic acid is much more active than are s/i-1 palmitoyl, stearoyl, or oleoyl.

Original languageEnglish (US)
Pages (from-to)1223-1232
Number of pages10
JournalClinical Cancer Research
Volume1
Issue number10
StatePublished - Oct 1 1995
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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