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CD9可能通过整合素功能的调节参与滋养层样绒毛膜癌细胞系BeWo的侵袭。本研究通过免疫组织化学研究了CD9是否在月经周期期间在子宫内膜中表达。在整个月经周期中，腺上皮细胞表面强烈表达，染色强度没有任何明显差异。此外，蛋白质印迹分析。亲和纯化的蛋白质证实CD9与人子宫内膜中的整合素β1、α3和α6相关，接下来检查的CD9的表达在子宫内膜增生的上皮细胞上呈阳性表达，但在子宫内膜腺癌中表达减少。为了了解子宫内膜癌中 CD9 表达降低的意义，使用体外侵袭测定系统来评估抗 CD9 单克隆抗体对子宫内膜癌侵袭特性的影响。抗CD9单克隆抗体显着增强RL95-2和Ishikawa细胞系的侵袭而不影响细胞增殖，因为CD9与人子宫内膜中的整合素β1、α3和α6相关，因此我们研究了CD9与这些细胞系之间的功能关系。子宫内膜癌细胞系 RL 95-2 中的整合素 针对整合素 β1、α3 和 α6 的单克隆抗体可抑制 RL。当用抗整合素α3单克隆抗体处理时，抗CD9单克隆抗体也显示出对RL 95-2细胞侵袭的刺激作用，相反，当用整合素α6和α6单克隆抗体处理时，它没有作用。这些发现表明CD9与子宫内膜癌细胞系的侵袭特性密切相关，这种参与部分是由整合素α6和β1介导的。 CD9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 involved in invasion of human trophoblast like choriocarcinoma cell line, Bewoells"Molecular Human Reproduction. 5・2. 168-174 (1999)

Takeshi Hirano 等人：“CD9 参与人类滋养层细胞（如绒毛膜癌细胞系 Bewoells）的侵袭”Molecular Human Reproductive 5·2（1999）。

Kyong Rim Park: "CD9 is expressed on human endometrial epithelial cells in association with integrins α6, α3 and β1."Mol Hum Reprod. 6. 252-257 (2000)

Kyong Rim Park：“CD9 在人子宫内膜上皮细胞上表达，与整合素 α6、α3 和 β1 相关。”Mol Hum Reprod. 6. 252-257 (2000)