| Project/Area Number |
18K08640
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 55020:Digestive surgery-related
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| Research Institution | Tohoku University |
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Principal Investigator |
fukase koji 東北大学, 医学系研究科, 大学院非常勤講師 (00578677)
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| 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)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
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| Keywords | 胆嚢癌 / CAF / GCF2 / 胆管癌 / 移動能 / 浸潤能 / 予後解析 / 癌転移制御 |
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| 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.
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| 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．
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