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Influence of growth factors on proliferation and morphogenesis of rabbit ovarian mesothelial cells in vitro.

The ovarian mesothelium (OM) is the source of one of the most frequent and lethal types of common ovarian epithelial tumors, the so-called papillary serous carcinomas. Recent work from our laboratory indicates the existence of postovulatory luteal OM mitogens with variable affinity for heparin. To further investigate the paracrine regulation of this ovarian tissue, rabbit ovarian mesothelial cells (OMC) were cultured in serum-free, fibronectin-rich HL-1 medium with or without one of the following luteal growth factors (0.1, 1, and 10 ng/ml): basic (bFGF) and acidic (aFGF) fibroblastic growth factors, epidermal growth factor (EGF), transforming growth factors alpha (TGF alpha) and beta (TGF beta), tumor necrosis factor alpha, platelet-derived growth factor (PDGF-BB), and vascular endothelial growth factor. After 8 days of culture, OMC growth was stimulated 3-fold by all tested doses of bFGF, EGF, and TGF alpha and 2-2.5-fold by 10 ng/ml of PDGF-BB and aFGF; it was inhibited more than 60% by TGF beta (10 ng/ml). In addition to enhancing the formation of cohesive OMC monolayers, most factors enhanced 3- to 6-fold the aggregation of OMC into papillary processes. The finding of a growth and morphogenetic response to intraluteal growth factors is novel and suggests a role for postovulatory paracrine regulation of OM pathobiology.