Unstable Expression of E‐Cadherin Adhesion Molecules in Metastatic Ovarian Tumor Cells

Abstract

E‐Cadherin is a member of the cadherin family, which plays a key role in intercellular adhesion in various tumors as well as in normal tissues. Here, we examined the expression of this adhesion molecule in a murine ovarian tumor line OV2944, whose sublines show different degrees of spontaneous metastasis from subcutaneous sites; sublines LM‐1 and LM‐3 exhibit a low metastatic activity but a variant subline HM‐1 has a high metastatic activity. When the expression of E‐cadherin in these cells was examined by immunoblot analysis, the highly metastatic HM‐1 cells was found to express an extremely small amount of this molecule, as compared with a high level of E‐cadherin expression in the weakly metastatic LM‐1 and LM‐3 cells. Northern blot analysis showed that the amount of tanscripts from the E‐cadherin gene is proportional to the amount of proteins detected in these cells. Immunofluorescence staining revealed that cells of the highly metastatic line were heterogeneous, that is, their cultures contained both E‐cadherin‐positive and negative cells. In contrast, cells of the weakly metastatic lines homogeneously expressed E‐cadherin. When the highly metastatic line was subcloned, all the subclones consisted of E‐cadherin‐positive and negative cells. These results suggest that the expression of E‐cadherin gene is not stably controlled in the highly metastatic line.

E-cadherin relates to EGFR expression and lymph node metastasis in primary breast carcinoma

“…One is that the cytoplasmic reactivity indicates a reversible change in Ecadherin expression by the cell in response to the local environment. It has been demonstrated that E-cadherin expression can easily be altered in vitro in response to the culture environment and that highly metastatic ovarian tumour cells have unstable E-cadherin expression (Hashimoto et al, 1989). Such a temporal disruption of E-cadherin-mediated adhesion would allow tumour cell detachment, while re-expression could favour colonisation at a distant site.…”

“…A more complex relationship has been observed between unstable or aberrant expression of cadherins and metastatic potential of tumour cells (Hashimoto et al, 1989;Mareel et al, 1991). While a clear role for E-cadherin in preventing tumour cell invasion has emerged from these in vitro studies, the relationship between E-cadherin expression in primary tumours and other prognostic parameters is inconsistent.…”

Soluble E-cadherin fragments increased in circulation of cancer patients

“…In contrast to the other cell-cell adhesive receptors, dysfunction in the regulation of cadherin expression might very well be involved in cancer development and progression (Takeichi, 1991;Umbas et al, 1992). Furthermore, E-cadherin is well known to be an invasive suppressor in tumour progressions, because expression levels for E-cadherins were reduced in almost all the malignant tumours and not correlated with their metastatic abilities (Behrens et al, 1989;Hashimoto et al, 1989). Additionally, a recent report suggested the possibility that some carcinoma cells lose E-cadherin expression during the process of detaching from the primary sites and infiltrating other sites (Matsuura et al, 1992); another elucidated that some Ecadherin functions expressed on the cancerous cell surfaces are impaired by loss or down-regulation of cytoplasmic proteins designated 'catenins' (Shimoyama et al, 1992).…”

“…E-cadherin, also termed uvomorulin or Cell-CAM120/80, is a cell-adhesive molecule found in epithelial cells in a variety of embryonic and adult tissues (Damsky et al, 1983;Ogou et al, 1983;Vestweber & Kemler, 1984). Several recent studies suggested that loss of E-cadherin may be associated with tumour progression in epidermal carcinogenesis as well (Navarro et al, 1991), and E-cadherin acts particularly as a suppressor of invasive ability (Behrens et al, 1989;Chen & Obrink, 1991;Frixen et al, 1991;Mareel et al, 1991;Vleminckx et al, 1991) or metastatic phenotype (Hashimoto et al, 1989;Schipper et al, 1991). In adult organisms, each cadherin displays a characteristic tissue distribution pattern, although expression is not tissue specific (Takeichi, 1991).…”

Dendritic Cell-Based Genetic Immunotherapy for Ovarian Cancer

“…HM-3 is a sub line of OV2944 which is a ovarian tumor cell line of B6C3F1 origin [31]. IG10 is a mouse ovarian cancer cell line of C57BL/6 origin [32].…”