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

(1)在子宫内膜癌中，E-钙粘附素功能丧失与高分化腺癌中E-钙粘附素和α-连环蛋白表达降低有关，在低分化腺癌中与α-连环蛋白和IQGAP1介导的黏附功能紊乱有关。在子宫内膜癌中，CD9和整粒-A3的表达降低与肿瘤的分级和有无淋巴结转移密切相关。多因素分析显示CD9的表达是影响子宫内膜癌预后的重要因素，提示细胞接触部位黏附分子的缺失在子宫内膜癌侵袭转移中起关键作用。(3)分析CD9和CD151在晚期卵巢癌细胞接触部位的表达。CD9表达缺失与耐药有关，CD151表达缺失与疾病进展密切相关。多因素分析显示，CD151的表达可作为晚期卵巢癌患者的预后因素。这些结果表明，细胞接触部位的Tetraspanins丢失可能是晚期卵巢癌耐药的分子机制之一。

(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.