Elucidation of the role of intracancerous fibroblasts in bile duct cancer malignancy and its application to new therapies
| Project/Area Number |
19K09133
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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 | Juntendo University |
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Principal Investigator |
imamura hiroshi 順天堂大学, 大学院医学研究科, 准教授 (00283268)
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| Co-Investigator(Kenkyū-buntansha) |
折茂 彰 順天堂大学, 大学院医学研究科, 教授 (70275866)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 胆管管 / CAFs / 癌微小環境 / オルガノイド / PDX / 胆管癌 / 癌内線維芽細胞 / 浸潤・転移 / 癌オルガノイド / ヒト胆管・膵癌 / 線維芽細胞 / 中間型上皮間葉移行 / PDXモデル / 治療法抵抗性 / 転移 / 浸潤 |
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| Outline of Research at the Start |
胆管癌の代表的な治療である手術療法、放射線療法や抗癌剤の効果は非常に限られているだけでなく、患者の生活の質を低下させる。それ故、より根治的な胆管癌の治療法の開発が望まれる。本研究では、胆管癌悪性化の原因を解明し新規治療開発に役立てるために、患者胆管癌手術検体を用いたpatient-derived tumor xenograft (PDX)モデルを樹立する。さらに、患者胆管癌由来CAFsを抽出し、胆管癌との共移植系PDXモデルを確立する。さらにCAFsが胆管癌の浸潤、転移や薬剤抵抗性に与える影響を解明し、CAFsと胆管癌の相互作用を媒介する遺伝子やシグナルを同定し、新規治療法の基礎を確立する。
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| 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.
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| 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。
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Report
(4 results)
Research Products
(5 results)
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[Journal Article] Laparoscopic cholecystectomy after endoscopic trans-papillary gallbladder stenting for acute cholecystitis: a pilot study of surgical feasibility2021
Author(s)
Kawano F, Yoshioka R, Gyoda Y, Ichida H, Mizuno T, Ishii S, Fujisawa T, Imamura H, Mise Y, Isayama H, Saiura A.
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Journal Title
BMC Surg.
Volume: 21
Issue: 1
Pages: 1-7
DOI
Related Report
Peer Reviewed
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