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A Putative New Growth Factor in Ascitic Fluid from Ovarian Cancer Patients: Identification, Characterization, and Mechanism of Action¹

Oncology Research, Toronto General Hospital, 200 Elizabeth Street, Toronto, Ontario, Canada M5G 2C4 [G. B. M., C. M., M. M.]; Division of Immunology and Rheumatology, Hospital For Sick Children, 555 University Avenue, Toronto, Ontario, Canada M5G 1X8 [C. M. R.]; and Department of Chemistry and Biochemistry, University of Guelph, Guelph, Ontario, Canada N1G 2W1 [A. M.]

Ascitic fluid from ovarian cancer patients (n = 16), but not from patients with other cancers or with benign diseases, contains a growth-promoting activity which induces the proliferation of both fresh ovarian cancer cells (n = 5) and the ovarian cancer cell line HEY. The ascitic fluid growth factor(s) appears to signal cells through binding and activation of specific, saturable, high-affinity cell surface receptors. Incubation of fresh or cultured ovarian cancer cells with a partially purified preparation of ascitic fluid stimulates phosphatidylinositol turnover and increases cytosolic-free calcium. Each of these biochemical events has been implicated in the action of growth factors. Purified preparations of previously identified growth factors including epidermal growth factor, transforming growth factor-ß, tumor necrosis factor, platelet-derived growth factor, thrombin, insulin, interleukin-1, interleukin-2, vasopressin, angiotensin, - and -interferons, and fibroblast growth factor did not increase cytosolic-free calcium in either fresh ovarian cancer cells or HEY cells. Therefore, ascitic fluid appears to contain one or more previously unidentified growth factors which activate ovarian cancer cells through phosphatidylinositol hydrolysis and resultant changes in cytosolic-free calcium.

¹ Supported by grants to G. B. M. from the National Cancer Institute of Canada, the Medical Research Council of Canada, and the Genesis Foundation of Canada.

² To whom requests for reprints should be addressed.

Received 8/11/87. Revised 11/20/87. Accepted 12/ 1/87.

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