Anti-CD9 monoclonal antibody-stimulated invasion of endometrial cancer cell lines in vitro: possible inhibitory effect of CD9 in endometrial cancer invasion

Cell surface marker CD9 has been reported to play a role in inhibiting trop hoblastic cell invasion. Since the invasive properties of cancer cells may resemble those of trophoblasts, we decided to investigate the role of CD9 i n the invasion of endometrial cancer cells. In normal human endometrium, CD 9 was found to be constitutively expressed on epithelial cells, as reported previously. While epithelial cells of endometrial hyperplasia (n = 5) were also positive for the expression of CD9, endometrial adenocarcinomas (n = 15) showed reduced expression. In order to clarify the significance of this reduced CD9 expression in endometrial cancer, an in-vitro invasion assay s ystem was used to assess the effect of anti-CDS monoclonal antibody (mAb) o n the invasive properties of endometrial cancer cell line. Anti-CDS mAb sig nificantly enhanced invasion of the RL95-2 and Ishikawa cell lines, without affecting cell proliferation. Since CD9 is associated with the integrin su bunits beta(1), alpha(3) and alpha(6) in human endometrium, we investigated the functional relationship between CD9 and these integrins in the RL95-2 cell line. Monoclonal antibodies against the integrins beta(1), alpha(3) an d as inhibited RL95-2 cell invasion. However, anti-CDS mAb continued to sho w a stimulatory effect on RL95-2 cell invasion after treatment with anti-in tegrin alpha(3) mAb. In contrast, the anti-CDS mAb had no effect after trea tment with the mAb for integrins alpha(6) and beta(1). These findings indic ate that CD9 is involved in regulating the invasive properties of endometri al carcinoma cells and that this effect is partially mediated by integrin s ubunits alpha(6) and beta(1). Thus, CD9 appears to be involved in the preve ntion of endometrial cancer invasion.