2020 Fiscal Year Final Research Report

Elucidation the mechanism of metastasis caused by GCF2 gene mutasion in bile duct cancer

Research Project

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Project/Area Number	18K08640
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 55020:Digestive surgery-related
Research Institution	Tohoku University
Principal Investigator	fukase koji 東北大学, 医学系研究科, 大学院非常勤講師 (00578677)
Co-Investigator(Kenkyū-buntansha)	有明恭平東北大学, 大学病院, 助教 (10754921) 大塚英郎東北大学, 大学病院, 講師 (50451563) 高舘達之東北大学, 高度教養教育・学生支援機構, 助教 (50772216) 海野倫明東北大学, 医学系研究科, 教授 (70282043)
Project Period (FY)	2018-04-01 – 2021-03-31
Keywords	胆嚢癌 / CAF
Outline of Final Research Achievements	In this study, we evaluated the metastatic potential induced by the cancer associated factor (CAF) of gallbladder cancer. CAF was established from surgical specimens of gallbladder cancer and fibroblasts (NF) were established from normal gallbladder tissue and their effects on mobility were evaluated. The mobility was enhanced in specific CAFs compared to NFs. It was shown that the Conditioned Medium (CM) from CAFs enhances the migration and invasion activity of gallbladder cancer cell lines. Microarray analysis revealed that Tenascin-C (TNC) and Podoplanin (PDPN) contribute to promote cell morbidity. Immunostaining showed that the recurrence-free survival and the overall survival were significantly poor in the cases with high expression of TNC and PDPN. From the above, it was shown that there are CAFs that express TNC and PDPN in gallbladder cancer and that they promote the progression of cancer.
Free Research Field	消化器外科
Academic Significance and Societal Importance of the Research Achievements	本研究により胆嚢癌のCAFを介した癌転移誘導メカニズムについて明らかになった．胆嚢癌は極めて予後不良な疾患であり，その原因として高い浸潤・転移能を有するといった特徴に加え，使用可能な抗癌剤の種類が乏しいことが挙げられる．本研究によってCAFを介した転移メカニズムの一つが解明され，転移形成を克服する上での新たな概念が提唱されたとともに，TNCとPDPNという抗癌剤治療の新規ターゲット因子の同定にもつなげることが可能となった．今後はCAFを介した転移メカニズムについての検討を行うとともに，TNCやPDPNといった新たな因子を標的とした治療法を開発することで，胆嚢癌の予後改善が期待される．