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

Abstract

Epithelial ovarian carcinomas arise in a simple mesothelium (ovarian surface epithelium, OSE) but exhibit properties of oviductal and endometrial epithelia. Thus, during malignant progression, their differentiation proceeds from 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 progression. The mechanisms underlying this process are not understood. Because cadherins are known regulators of differentiation, we investigated the relationship of the cadherins E, N and P to OSE morphology, growth patterns and differentiation in cultures of normal and metaplastic OSE from women with (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‐cadherin as the constitutively expressed cadherin of normal and metaplastic OSE and indicate that P‐cadherin is undetectable while E‐cadherin expression is conditional and related to genotype, stage of neoplastic progression and growth pattern. The altered expression of E‐cadherin in apparently normal OSE of women with hereditary ovarian cancer syndromes in conjunction with the known capacity of E‐cadherin to induce epithelial characteristics implicates this adhesion molecule as a possible inducer of the aberrant Mullerian differentiation which characterizes epithelial ovarian carcinomas. Abnormal differentiation in such (pre)‐neoplastic tissues may represent an early, irreversible, non‐mutational step in ovarian epithelial neoplastic progression. Int. J. Cancer 81:180–188, 1999. © 1999 Wiley‐Liss, Inc.

Primary cilia and aberrant cell signaling in epithelial ovarian cancer

“…OSE cells possess primary cilia, as visualized with antibodies against two well-characterized ciliary markers, acetylated α-tubulin (Acet.tub) and detyrosinated α-tubulin (Glu.tub) (Figure 1A, lower insert) as described earlier [56]. Further, consistent with previous observations [57-59], we found that OSE has a limited commitment to the epithelial phenotype indicated by the retention of mesenchymal features, such as expression of vimentin and N-cadherin, and it lacks some of the typical epithelial characteristics, such as E-cadherin (Figure 1B-D).…”

N-Cadherin Dependent Collective Cell Invasion of Prostate Cancer Cells Is Regulated by the N-Terminus of α-Catenin

“…However, during embryogenesis, neuro crest cell migration is initiated by the down-regulation of N-cadherin [28], therefore, the N-cadherin level is not the sole determinant of the cell migratory phenotype in all processes. Consistent with this notion, an N to E-cadherin switch occurs in ovarian cancer [29], [30] while the expression of cadherin 11 has been shown to suppress cell migration [31]. Ectopic expression of new cadherins along with other cadherin regulators may be the key to controlling cell-cell adhesion of migratory cells.…”

N-cadherin is differentially expressed in histological subtypes of papillary renal cell carcinoma

“…It is widely accepted that an increased expression of E-cadherin in cancer is associated with a better outcome and a decrease occurrence of metastases [13]; in ovarian carcinoma lower E-cadherin seems to influence the transition from normal ovarian surface epithelium to ovarian cancer [36]. The investigation of KSP-cadherin showed only a weak membranous and cytoplasmic expression in both subtypes of papillary RCC.…”