The significance of high claudin expression in ovarian cancer

Research Project

Project/Area Number	17K17981
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Multi-year Fund
Research Field	Obstetrics and gynecology Tumor biology
Research Institution	Fukushima Medical University
Principal Investigator	KOJIMA MANABU 福島県立医科大学, 医学部, 博士研究員 (30746970)
Project Period (FY)	2017-04-01 – 2020-03-31
Project Status	Completed (Fiscal Year 2019)
Budget Amount *help	¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000) Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000) Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000) Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords	子宮内膜癌 / 核内受容体 / シグナル伝達 / クローディン / エストロゲン受容体 / 接着分子 / エストロゲン / 細胞間接着分子 / エストロゲンレセプター / 卵巣癌 / 癌
Outline of Final Research Achievements	Regarding the clinicopathologic significance of high expression of claudin-6 in ovarian cancer, the number of cases was reexamined and no significant difference was obtained. On the other hand, a simultaneous study of endometrial cancer found that high expression of claudin 6 was strongly associated with 5-year survival, suggesting that claudin-6 is a strong poor prognostic factor in endometrial cancer. It was In addition, molecular biology revealed that claudin-6 overexpressing strains showed higher proliferation and migration abilities than wild strains, that they were associated with estrogen receptor α to enhance malignant phenotypes, and estrogen receptor the phosphorylation site required for the activation of was identified.
Academic Significance and Societal Importance of the Research Achievements	婦人科癌の殺細胞剤の奏効率はタキサン・プラチナ製剤の出現によって飛躍的に向上したが、進行例の再発率は依然として高い。新たに開発された分子標的薬も全生存期間を有意に改善しないばかりか、腸管穿孔や血栓症等の有害事象が問題視されている。このようにいくつかの課題を抱える薬物療法の現状を鑑みると、細胞間接着分子クローディン6は腫瘍のみに発現する際だった特徴もつため、クローディン6を標的とする抗体薬を用いた治療戦略は理想的といえる。今後はクローディン-6抗体薬の作成やクローディン6を検出するコンパニオン診断薬の開発につながる成果を示したい。