Investigation of the effect of CD9 on endometrial cancer cell invasion

CD9对子宫内膜癌细胞侵袭能力的影响研究

• 批准号: 11671614
• 负责人: INOUE Takuya
• 金额: $ 1.02万
• 依托单位: KYOTO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11671614/
• 关键词: Endometrial cancer; Cancer invasion; CD9; 子宮内膜; インテグリン; 細胞浸潤

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.

最近，我们报道了CD 9可能通过调节整合素功能参与滋养层样绒毛膜癌细胞系BeWo的侵袭。本研究采用免疫组化方法研究了月经周期中子宫内膜是否表达CD 9。发现CD 9在整个月经周期的腺上皮细胞表面上强烈表达，染色强度没有任何明显差异。免疫印迹分析证实，CD 9与整合素β1、α3和α6在人子宫内膜中存在相关性。CD 9在子宫内膜增生过长的上皮细胞中呈阳性表达，而在子宫内膜腺癌中表达减弱。为了阐明CD 9表达降低在子宫内膜癌中的意义，使用体外侵袭测定系统来评估抗CD 9单克隆抗体对子宫内膜癌细胞系的侵袭特性的影响。抗CD 9单克隆抗体可显著增强RL 95 -2和石川细胞系的侵袭能力，但不影响细胞增殖。由于CD 9与人子宫内膜中的整合素β 1、α3和α6相关，我们研究了CD 9与子宫内膜癌细胞系RL 95-2中这些整合素之间的功能关系。抗整合素β1、α3和α6单克隆抗体可抑制RL 95-2细胞的侵袭。抗整合素α3单克隆抗体处理RL 95-2细胞后，抗CD 9单克隆抗体对RL 95-2细胞的侵袭也有促进作用。相反，当用整合素α6和β 1的单克隆抗体处理时，它没有效果。这些结果表明，CD 9是深入参与子宫内膜癌细胞系的侵袭特性。这种参与部分由整合素α6和β1介导，这表明CD 9可能参与预防子宫内膜癌侵袭。

项目成果

Kyong Rim Park,Takuya Inove,Masamichi Ueda, et al.: "Anti-CD9 monoclonal antibody-stimulated invasion of endometrial cancer cell lines in vitro : possible inhibitory effect of CD9 in endometrial cancer invasion"Molecular Human Reproduction. 6・8. 719-725 (

Kyong Rim Park、Takuy​​a Inove、Masamichi Ueda 等人：“抗 CD9 单克隆抗体刺激子宫内膜癌细胞系的体外侵袭：CD9 对子宫内膜癌侵袭的可能抑制作用”分子人类生殖 6・8。 -725（

Shigetoshi Yamada, et al.: "Human granulosa cells express integrin α2 and collagen.type IV : possible involvement cof collagen type IV in granulosa cell Inteinization."Molecular Human Reproduction. 5・7. 607-617 (1999)

Shigetoshi Yamada 等人：“人类颗粒细胞表达整合素 α2 和 IV 型胶原蛋白：IV 型胶原蛋白可能参与颗粒细胞内嵌化”。《分子人类生殖》607-617。

Kyong Rim Park: "Anti-CD9 monoclonal antibody-stimulated invasion of endometrial cancer cell lines in vitro : possible inhibitory effect of CD9 in endometrial cancer invasion."Mol Hum Reprod. 8. 719-725 (2000)

Kyong Rim Park：“抗 CD9 单克隆抗体在体外刺激子宫内膜癌细胞系的侵袭：CD9 在子宫内膜癌侵袭中可能具有抑制作用。”Mol Hum Reprod。

Takeshi Hirano, et al.: "CD9 is expressed in extravillous trophoblasts and associated with Integrin α3 and integrin α5"Molecular Human Reproduction. 5・2. 162-167 (1999)

Takeshi Hirano 等人：“CD9 在绒毛外滋养细胞中表达，并与整合素 α3 和整合素 α5 相关”《分子人类生殖》162-167。

Hiroshi Fujiwara: "Membrane-bound cell surface peptidases in reproductive organs."Endocrine Journal.. 46. 11-25 (1999)

Hiroshi Fujiwara：“生殖器官中的膜结合细胞表面肽酶。”内分泌杂志.. 46. 11-25 (1999)