Isolation of cancer stem cells of cholangiocarcinoma and identification of new therapeutic targets of cholangiocarcinoma

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K10592
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Kyoto University
• Principal Investigator: Ishii Takamichi 京都大学, 医学研究科, 特定病院助教 (70456789)
• Co-Investigator(Kenkyū-buntansha): 安近 健太郎 京都大学, 医学研究科, 客員研究員 (00378895) ; 上本 伸二 京都大学, 医学研究科, 教授 (40252449) ; 河合 隆之 京都大学, 医学研究科, 客員研究員 (00813867)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 転移能 / 胆管癌 / 上皮間葉転換

Outline of Final Research Achievements

Expression of CD90 has been reported as a poor prognostic factor in many cancer types. The purpose of this study was to investigate the significance of CD90 expression in intrahepatic cholangiocarcinoma.
In the intrahepatic cholangiocarcinoma surgical specimens, the expression of CD90 was observed in 25 of 77 cases. The CD90 expression was significantly correlated with lymph node metastasis, and the CD90 expression was one of the independent prognostic factors. Analysis of human intrahepatic cholangiocarcinoma cell lines revealed that the isolated CD90-expressing cells highly expressed epithelial-mesenchymal transition related genes via activated Wnt /b-catenin signaling, resulting in a high metastatic potential. Therefore, it is thought that the increased risk of lymph node metastasis related to poor prognosis in the CD90-expressing intrahepatic cholangiocarcinoma.

Free Research Field

肝胆膵外科学

Academic Significance and Societal Importance of the Research Achievements

本研究ではCD90発現胆管癌細胞はin vitroではWnt/b-catenin signalingを介してEMT関連遺伝子を高発現し高い転移能を有しており，in vivoではリンパ節転移のリスクが高くなり予後不良に関与していた．この成果によりCD90陽性胆管細胞癌の転移メカニズムの一端が明らかされ，Wnt/b-catenin pathwayという胆管細胞癌に対する新規治療ターゲットが同定できた．このことによりCD90発現の有無によって治療戦略が異なり個別化医療へと繋がる可能性が示されたと考え，社会的意義を有すると思われる．