E-cadherin expression in human epithelial ovarian cancer and normal ovary

Sundfeldt, Karin; Piontkewitz, Yael; Ivarsson, Karin; Nilsson, Ola; Hellberg, Pår; ouml:m, Mats Brännstr; Janson, Per-Olof; Enerbäck, Sven; Hedin, Lars O.

doi:10.1002/(sici)1097-0215(19970620)74:3<275::aid-ijc7>3.0.co;2-w

Cited by 156 publications

(113 citation statements)

References 21 publications

(44 reference statements)

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“…In fact, both Nand E-cadherin can reduce or block the transcriptional activity of b-catenin/Lef1, relocate b-catenin to the cell border and inhibit the degradation of b-catenin (Sadot et al, 1998). We and others have earlier demonstrated that E-cadherin is induced during the progression of ovarian epithelial tumours (Sundfeldt et al, 1997;Auersperg et al, 2001). The elevated expression of E-cadherin in ovarian cancer could increase binding of b-catenin to the plasma membrane.…”

Section: Discussionmentioning

confidence: 97%

“…The downregulation of cadherins or dysfunction of the cadherincatenin complex has been noted in different types of tumours. In the human ovary, neuronal (N) cadherin, but not epithelial (E) cadherin, is expressed in the normal ovarian surface epithelium (OSE) (Sundfeldt et al, 1997;Auersperg et al, 2001). However, Ecadherin is upregulated in inclusion cysts of the normal ovary and in ovarian tumours with invasive capacity (Sundfeldt et al, 1997;Auersperg et al, 2001).…”

mentioning

confidence: 99%

“…In the human ovary, neuronal (N) cadherin, but not epithelial (E) cadherin, is expressed in the normal ovarian surface epithelium (OSE) (Sundfeldt et al, 1997;Auersperg et al, 2001). However, Ecadherin is upregulated in inclusion cysts of the normal ovary and in ovarian tumours with invasive capacity (Sundfeldt et al, 1997;Auersperg et al, 2001). At the protein level, both a-and b-catenin are expressed in normal OSE and invasive ovarian tumours (Auersperg et al, 2001 types of ovarian tumours (Gamallo et al, 1999;Wright et al, 1999).…”

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confidence: 99%

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Wnt-signalling pathway in ovarian epithelial tumours: increased expression of β-catenin and GSK3β

et al. 2003

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Beta-catenin is involved in both cell -cell adhesion and in transcriptional regulation by the Wingless/Wnt signalling pathway. Alterations of components of this pathway have been suggested to play a central role in tumorigenesis. The present study investigated, by immunohistochemistry and immunoblotting, the protein expression and localisation of b-catenin, adenomatous polyposis coli (APC), glycogen synthase kinase 3b (GSK3b) and lymphocyte enhancer factor-1 (Lef-1) in normal human ovaries and in epithelial ovarian tumours in vivo and in vitro. Immortalised human ovarian surface epithelium and ovarian cancer cell cells (OVCAR-3) expressed b-catenin, APC, GSK3b and Lef-1. Nuclear staining of b-catenin and Lef-1 were demonstrated only in OVCAR-3 cells. There were significant increases of b-catenin and GSK3b, while APC was reduced in ovarian cancer compared to the normal ovary. Beta-catenin and Lef-1 were coimmunoprecipitated in ovarian tumours, but not in the normal ovary. Nuclear localisation of b-catenin or Lef-1 could not be demonstrated in the normal ovary or in the ovarian tumours. The absence of nuclear localisation of b-catenin could be due to an increased binding to the cadherin -a-catenin cell adhesion complex. In fact, we have earlier reported an increased expression of E-cadherin in ovarian adenocarcinomas. In summary, this study demonstrates an increase in the expression of components of the Wingless/Wnt pathway in malignant ovarian tumours. The increase suggests a role for this signalling pathway in cell transformation and in tumour progression. However, it remains to be demonstrated whether it is an increased participation of b-catenin in transcriptional regulation, or in the stabilisation of cellular integrity, or both, that is the crucial event in ovarian tumorigenesis.

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Section: Discussionmentioning

confidence: 97%

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Wnt-signalling pathway in ovarian epithelial tumours: increased expression of β-catenin and GSK3β

et al. 2003

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“…In tissue culture, OSE cells express epithelial markers including keratin, desmosomes, tight junctions, laminin, basement membrane type IV collagen and apical microvilli, as well as mesenchymal markers such as vimentin and interstitial collagen types I and III [13,14]. The mesodermally derived OSE expresses unusually low levels of the epithelial cell-cell adhesion molecule E-cadherin [13,15], with expression limited to inclusion cysts or deep clefts [16] where early malignant changes are believed to occur [16,17]. In contrast to other epithelia, OSE epithelial integrity is maintained primarily by neural-(N)-cadherin, consistent with the epithelial-mesenchymal phenotype of this tissue [13,[18][19][20].…”

Section: Normal and Neoplastic Ovarian Epitheliummentioning

confidence: 99%

“…E-Cadherin-An unique feature of EOC is that E-cadherin becomes more abundant in primary differentiated ovarian carcinomas [16,18,20,51,53,[56][57][58][59], with all histotypes displaying strong immunoreactivity. Our data demonstrate positive E-cadherin staining in 86% of tumors analyzed (n=146) with strong immunoreactivity in 73%, consistent with a gain of epithelial phenotype [ Table 1, Fig.…”

Section: B Cadherin Expression In Eocmentioning

confidence: 99%

Phenotypic plasticity of neoplastic ovarian epithelium: unique cadherin profiles in tumor progression

Hudson

Zeineldin

Stack

2008

Clin Exp Metastasis

165

172

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The mesodermally derived normal ovarian surface epithelium (OSE) displays both epithelial and mesenchymal characteristics and exhibits remarkable phenotypic plasticity during post-ovulatory repair. The majority of epithelial ovarian carcinomas (EOC) are derived from the OSE and represent the most lethal of all gynecological malignancies, as most patients (~70%) present at diagnosis with disseminated intra-abdominal metastasis. The predominant pattern of EOC metastasis involves pelvic dissemination rather than lymphatic or hematologic spread, distinguishing EOC from other solid tumors. Acquisition of the metastatic phenotype involves a complex series of interrelated cellular events leading to dissociation (shedding) and dispersal of malignant cells. A key event in this process is disruption of cell-cell contacts via modulation of intercellular junctional components. In contrast to most carcinomas that downregulate E-cadherin expression during tumor progression, an unique feature of primary well-differentiated ovarian cancers is a gain of epithelial features, characterized by an increase in expression of E-cadherin. Subsequent reacquisition of mesenchymal features is observed in more advanced tumors with concomitant loss of E-cadherin expression and/ or function during progression to metastasis. The functional consequences of this remarkable phenotypic plasticity are not fully understood, but may play a role in modulation of cell survival in suspension (ascites), chemoresistance, and intraperitoneal anchoring of metastatic lesions. Keywords ovarian cancer; epithelium; cadherin; keratin; vimentin; epithelial-mesenchymal transition; plasticity Ovarian Cancer-OverviewTumors arising from the ovarian epithelium account for ~90% of ovarian malignancies and epithelial ovarian carcinoma (EOC) is the leading cause of death from gynecologic malignancy, resulting in approximately 15,280 deaths in the United States alone in 2006 [1]. These distressing statistics are largely due to the low detection rate of disease confined to the ovary (stage 1) when 5-year survival is >90%. Approximately 75% of women are initially diagnosed with disseminated intra-abdominal disease (stage III-IV) and have a 5-year survival of <20%.Ovarian tumors are pathologically heterogeneous with four major histotypes: serous, endometroid, clear cell and mucinous. These classifications are histogenetically based on The early steps of EOC metastasis involve shedding of the cells from the primary tumor to form free floating cells or multi-cellular aggregates (MCAs) in ascites [ Fig. 1]. Cell-cell and cell-matrix adhesion molecules mediate interaction of metastasizing tumor cells with mesothelial cells lining the inner surface of the peritoneal cavity and the sub-mesothelial extracellular matrix (ECM). Localized proteolytic degradation of sub-mesothelial ECM components facilitates migration of tumor cells and anchoring of secondary lesions on adjacent pelvic organs, and at later stages, metastasis to distant organs [9,10]. However, the majority of wo...

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

Wong

Maines-Bandiera

Rosen³

et al. 1999

Int. J. Cancer

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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.

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E-cadherin expression in human epithelial ovarian cancer and normal ovary

Cited by 156 publications

References 21 publications

Wnt-signalling pathway in ovarian epithelial tumours: increased expression of β-catenin and GSK3β

Wnt-signalling pathway in ovarian epithelial tumours: increased expression of β-catenin and GSK3β

Phenotypic plasticity of neoplastic ovarian epithelium: unique cadherin profiles in tumor progression

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

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