Elucidation of the role of intracancerous fibroblasts in bile duct cancer malignancy and its application to new therapies

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K09133
• 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: Juntendo University
• Principal Investigator: imamura hiroshi 順天堂大学, 大学院医学研究科, 准教授 (00283268)
• Co-Investigator(Kenkyū-buntansha): 折茂 彰 順天堂大学, 大学院医学研究科, 教授 (70275866)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 胆管管 / CAFs / 癌微小環境 / オルガノイド / PDX

Outline of Final Research Achievements

Carcinoma-associated fibroblasts (CAFs), which are abundant in the stroma of cholangiocarcinoma, are involved in infiltration of cancer cells, promotion of metastasis, and acquisition of treatment resistance, but the molecular mechanism remains unclear. In this study, in order to clarify roles of CAFs on cholangiocarcinoma progression, specimens of bile duct cancer and non-cancerous parts removed by surgery were collected in 5 cases, and 4 cases of CAFs and control fibers were successfully collected by primary culture. Five cases of bile duct cancer were transplanted into highly immunodeficient NOG mice, but no cancer growth was observed. In the future, we would like to increase the number of cases by establishing cancer organoids directly from clinical specimens and try to identify genes and signals that mediate the interaction between CAFs and bile duct cancer cells.

Free Research Field

消化器外科

Academic Significance and Societal Importance of the Research Achievements

本研究において、申請者らはCAFsが近傍の癌細胞にpartial EMT（epithelial-mesenchymal transition）を誘導する可能性に注目している。partial EMTが細胞―細胞接着を維持した癌細胞クラスターの形成および間葉系の表現型を誘導し、癌細胞の浸潤・転移能や治療抵抗性能を促進させる可能性を提案した。本研究が成功した場合は、CAFsによる新規の浸潤・転移能や治療抵抗性能促進メカニズムを解明できる可能性がある。