Investigation of the effect of CD9 on endometrial cancer cell invasion

点击翻译按钮获取中文摘要

Recently we reported that CD9 is involved in the invasion of a trophoblast-like choriocarcinoma cell line, BeWo, probably through the regulation of integrin functions. This study investigated immunohistochemically whether CD9 is expressed in the endometrium during the menstrual cycle. CD9 was found to be intensely expressed on the cell surface of the glandular epithelium throughout the menstrual cycle without any apparent differences in staining intensity. In addition, western blotting analysis of the affinity-purified proteins confirmed that CD9 was associated with integrin β1, α3 and α6 in the human endometrium. Next, the expression of CD9 examined showed positive expression on the epithelial cells of endometrial hyperplasia, but reduced expression in endometrial adenocarcinomas. In order to clarify the significance of the reduced CD9 expression in endometrial cancer, an in vitro invasion assay system was used to assess the effect of anti-CD9 monoclonal antibody on the invasive properties of endometrial cancer cell lines. Anti-CD9 monoclonal antibody significantly enhanced invasion of RL95-2 and Ishikawa cell line without affecting cell proliferation. Since CD9 is associated with integrins βl, α3 and α6 in human endometrium, we investigated the functional relationship between CD9 and these integrins in endometrial cancer cell line RL 95-2. Monoclonal antibodies against the integrins β1, α3 and α6 inhibited RL 95-2 cell invasion. Anti-CD9 monoclonal antibody also showed a stimulatory effect on RL 95-2 cell invasion when treated with anti-integrin α3 monoclonal antibody. In contrast, it had no effect when treated with the monoclonal antibodies for integrin α6 and βl. These findings indicate that CD9 is deeply involved in the invasive properties of endometrial carcinoma cell line. This involvement is partially mediated by integrin α6 and β1, which suggests the possible involvement Of CD9 in the prevention of endometrial cancer invasion.