Cell biology of human ovarian surface epithelial cells and ovarian carcinogenesis

Abstract

Most epithelial ovarian carcinomas have been suggested to arise from the ovarian surface epithelium, which covers an ovary as a layer of flat to cuboidal cells. The epithelium is physiologically involved in follicular rupture and the subsequent repair of the follicle wall during reproductive age. Invagination and inclusion cysts are formed in the cortical stroma after cyclic ovulation. Consequently, ovulation may cause a loss of integrity of the surface epithelium followed by stepwise sequence of genetic alteration. Inclusion cysts are actually more common in ovaries contralateral to those containing malignant epithelial tumors than in control ovaries. Human ovarian surface epithelial cells exhibit a gland formation in coculture with endometrial stromal cells in an estrogen-rich environment. The phenotypic plasticity of these cells shares a mesenchymal property when they are cultured on two layers of extracellular matrix and collagen gel. As an in vitro study of ovarian carcinogensis, several neoplastic cell lines were recently established from the surface epithelial cells of the human ovary. SV 40 large T-antigen transfection into the epithelial cells induced some immortalized cell lines, one of which showed anchorage-independent growth and tumor formation in athymic mice. The tumors were histologically undifferentiated carcinoma. These cell lines may lead to insights into the preneoplastic and early stages of epithelial ovarian carcinomas. To understand the pathogenesis of epithelial ovarian cancer, specifically designed studies of ovarian surface epithelium and the related structural changes encountered after ovulation and these existing in ovarian carcinomas are required.