Constitutive production of interleukin 6 by ovarian cancer cell lines and by primary ovarian tumor cultures.
We examined the production and utilization of interleukin 6 (IL-6), a multifunctional cytokine with diverse biological effects, by both ovarian cancer cell lines and primary ovarian tumor cultures. We have found that epithelial ovarian cancer cell lines (CAOV-3, OVCAR-3, and SKOV-3) constitutively produce varying amounts of IL-6. This molecule is biologically active as determined by the proliferation of an IL-6-dependent hybridoma cell line, MH60.BSF-2, and is detectable by an IL-6 enzyme-linked immunosorbent assay. By cytoplasmic immunoperoxidase staining, greater than 98% of the cells produce at least some IL-6, with variation in the staining intensity between individual cells. The ovarian cancer cell-produced protein has a molecular weight of approximately 24,000, and exhibits some molecular weight heterogeneity, with Mr 27,000 and 28,000 minor forms of IL-6. The levels of IL-6 produced by ovarian cancer cells can be modulated by other inflammatory cytokines, such as tumor necrosis factor-alpha, interleukin-1 beta, and interferon-gamma. Our results suggest that IL-6 is not an autocrine growth factor for these established ovarian tumor cell lines, because the addition of either exogenous IL-6 or antibodies to IL-6 did not affect the cellular proliferation of the cell lines. We also found significant levels (greater than 3 ng/ml) of IL-6 in ascitic fluids of ovarian cancer patients and in the supernants of primary cultures from freshly excised ovarian tumors. The production of IL-6 by epithelial ovarian cancer cells may prove to be a useful diagnostic tool and aid in investigation of the host immune response to ovarian cancer.
Department of Microbiology and Immunology, University of California-Los Angeles School of Medicine 90024.
J M
JM
Watson
J L
JL
Sensintaffar
J S
JS
Berek
O
O
Martínez-Maza
D002455:Cell Division / Q000187:drug effects; D004848:Epithelium / Q000378:metabolism; D005260:Female; D006133:Growth Substances / Q000502:physiology; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000378:metabolism / Q000494:pharmacology; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology; D011994:Recombinant Proteins / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D006133:Growth Substances; D015850:Interleukin-6; D011994:Recombinant Proteins