Constitutive and conditional cadherin expression in cultured human ovariansurface epithelium: Influence of family history of ovarian cancer

Epithelial ovarian carcinomas arise In a simple mesothelium (ovarian surfac e epithelium, OSE) but exhibit properties of oviductal and endometrial epit helia, Thus, during malignant progression, their differentiation proceeds f rom simple to complex, in contrast to carcinomas in other tissues. Related changes in OSE of women with a history of familial ovarian cancer indicate that this aberrant differentiation Is initiated very early in neoplastic pr ogression. The mechanisms underlying this process are nor understood. Becau se cadherins are known regulators of differentiation, we investigated the r elationship of the cadherins E, N and P to OSE morphology, growth patterns and differentiation in cultures of normal and metaplastic OSE from women wi th (FH-OSE) and without (NFH-OSE) a family history of ovarian cancer and in the ovarian carcinoma lines OVCAR-3 and CaOV3, We used Immunofluorescence, RT-PCR, in situ hybridization and Western blotting, Our results define N-c adherin as the constitutively expressed cadherin of normal and metaplastic OSE and indicate that P-cadherin is undetectable while E-cadherin expressio n is conditional and related to genotype, stage of neoplastic progression a nd growth pattern, The altered expression of E-cadherin in apparently norma l OSE of women with hereditary ovarian cancer syndromes in conjunction with the known capacity of E-cadherin to induce epithe lial characteristics Imp licates this adhesion molecule as a possible inducer of the aberrant Muller ian differentiation which characterizes epithelial ovarian carcinomas. Abno rmal differentiation in such (pre)-neoplastic tissues may represent an earl y, irreversible, non-mutational step in ovarian epithelial neoplastic progr ession. Int. J. Cancer 81: 180-188, 1999. (C) 1999 Wiley-Liss, Inc.