Park K R, Inoue T, Ueda M, Hirano T, Higuchi T, Konishi I, Fujiwara H, Fujii S
Department of Gynaecology and Obstetrics, Faculty of Medicine, Institute for Virus Research, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan.
Mol Hum Reprod. 2000 Aug;6(8):719-25. doi: 10.1093/molehr/6.8.719.
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 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) and alpha(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 alpha(3) mAb. In contrast, the anti-CD9 mAb had no effect after treatment with the mAb for integrins alpha(6) and beta(1). 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 alpha(6) and beta(1). Thus, CD9 appears to be involved in the prevention of endometrial cancer invasion.
据报道，细胞表面标志物CD9在抑制滋养层细胞侵袭中发挥作用。由于癌细胞的侵袭特性可能类似于滋养层细胞，我们决定研究CD9在子宫内膜癌细胞侵袭中的作用。正如之前报道的那样，在正常人类子宫内膜中，发现CD9在上皮细胞中组成性表达。虽然子宫内膜增生（n = 5）的上皮细胞CD9表达也呈阳性，但子宫内膜腺癌（n = 15）显示表达降低。为了阐明子宫内膜癌中CD9表达降低的意义，使用体外侵袭分析系统评估抗CD9单克隆抗体（mAb）对子宫内膜癌细胞系侵袭特性的影响。抗CD9 mAb显著增强了RL95 - 2和Ishikawa细胞系的侵袭能力，而不影响细胞增殖。由于CD9在人类子宫内膜中与整合素亚基β(1)、α(3)和α(6)相关联，我们研究了RL95 - 2细胞系中CD9与这些整合素之间的功能关系。针对整合素β(1)、α(3)和α(6)的单克隆抗体抑制了RL95 - 2细胞的侵袭。然而，在用抗整合素α(3) mAb处理后，抗CD9 mAb对RL95 - 2细胞侵袭仍显示出刺激作用。相反，在用整合素α(6)和β(1)的mAb处理后，抗CD9 mAb没有效果。这些发现表明，CD9参与调节子宫内膜癌细胞的侵袭特性，并且这种作用部分由整合素亚基α(6)和β(1)介导。因此，CD9似乎参与了对子宫内膜癌侵袭的预防。
