Biological Roles of Integrin Signal Transduction at Cell-Cell Contact in the Invasion and Metastasis of Endometrial Cancer

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(1) In endometrial cancer, the loss of function of E-cadherin was associated with a decrease of E-cadherin and α-catenin expression in well differentiated adenocarcinoma and was involved in disturbance of adhesiveness as well as detachment mediated by α-catenin and IQGAP1 in poorly differentiated adenocarcinoma.(2) CD9 and integrin-a3 regulate cell-cell adhesion in epithelial cells. In endometrial cancer, the decrease of CD9 and integrain-a3 expression was significantly correlated with the grade of a tumor and metastasis of lymph nodes. The multivariated analysis disclosed that the expression of CD9 was considered as a significantly prognostic factor.These results suggested that the loss of adhesion molecules at cell contact sites plays a pivotal role in acquirement of invasive and metastatic properties in endometrial cancer.(3) In advanced ovarian cancer, we analyzed the expression of CD9 and CD151 localized at cell contact sites. The loss of CD9 expression was associated with drug resistance, and the loss of CD151 expression was significantly involved in the progression of disease. The multivariated analysis revealed that the expression of CD151 was regarded as a prognostic factors in patients with advanced ovarian cancer. These results suggested that the loss of tetraspanins at cell contact sites may contribute to molecular mechanisms for drug resistance in advanced ovarian cancer.