Molecular Human Reproduction, Vol. 6, No. 8, 719-725,
August 2000
© 2000 European Society of Human Reproduction and Embryology
Uterine physiology |
Anti-CD9 monoclonal antibody-stimulated invasion of endometrial cancer cell lines in vitro: possible inhibitory effect of CD9 in endometrial cancer invasion
1 Department of Gynaecology and Obstetrics, Faculty of Medicine, 2 Institute for Virus Research, Kyoto University, Sakyo-ku, Kyoto 606-8507, and 3 Department of Gynaecology and Obstetrics, Shinshu University School of Medicine, Asahi, Matsumoto 390-8621, Japan
Abstract
Cell surface marker CD9 has been reported to play a role in inhibiting trophoblastic cell invasion. Since the invasive properties of cancer cells may resemble those of trophoblasts, we decided to investigate the role of CD9 in the invasion of endometrial cancer cells. In normal human endometrium, CD9 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 system was used to assess the effect of anti-CD9 monoclonal antibody (mAb) on the invasive properties of endometrial cancer cell line. Anti-CD9 mAb significantly enhanced invasion of the RL95-2 and Ishikawa cell lines, without affecting cell proliferation. Since CD9 is associated with the integrin subunits ß1, 
3 and 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 ß1, 3 and 6 inhibited RL95-2 cell invasion. However, anti-CD9 mAb continued to show a stimulatory effect on RL95-2 cell invasion after treatment with anti-integrin 3 mAb. In contrast, the anti-CD9 mAb had no effect after treatment with the mAb for integrins 6 and ß1. These findings indicate that CD9 is involved in regulating the invasive properties of endometrial carcinoma cells and that this effect is partially mediated by integrin subunits 6 and ß1. Thus, CD9 appears to be involved in the prevention of endometrial cancer invasion.
CD9/endometrium/endometrial cancer/integrin/invasion
Notes
4 To whom correspondence should be addressed at: Department of Gynaecology and Obstetrics, Faculty of Medicine, Kyoto University, Sakyo-ku, Kyoto, 606-8507, Japan. E-mail: fuji{at}kuhp.kyoto-u.ac.jp
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