| Project/Area Number |
18K15797
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 53010:Gastroenterology-related
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| Research Institution | Juntendo University |
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Principal Investigator |
suzuki mayu 順天堂大学, 医学部, 非常勤助手 (90815341)
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| Project Period (FY) |
2018-04-01 – 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: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
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| Keywords | 食道癌 / 浸潤・転移 / 癌悪性化 / CAFs / 癌微小環境 / オルガノノイド / 治療抵抗異性 / PDXモデル / 食道がん / 線維芽細胞 / CAFｓ / PDXマウス / 患者食道癌 / 治療法抵抗性 / 治療抵抗性 / 薬剤耐性 / PDX model |
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| Outline of Final Research Achievements |
CAFs, which are abundant in esophageal cancer stroma, are involved in cancer cell infiltration, promotion of metastasis, and acquisition of treatment resistance, but the molecular mechanism remains unclear. In the submitted study, specimens of esophageal cancer and non-cancerous areas removed by surgery were collected from 33 cases and primary culture was performed, and CAFs and control fibroblasts were successfully established in 27 cases. In addition, 5 cases of esophageal cancer organoids were also established. In the future, we plan to use co-culture and co-transplanted mouse models of these patient-derived fibroblasts and esophageal cancer organoids to investigate genes and signaling that contribute to cancer malignancy at the molecular level.
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| Academic Significance and Societal Importance of the Research Achievements |
申請者らはCAFsとの相互作用により近傍の食道癌細胞にpartial EMT（epithelial-mesenchymal transition）が誘導され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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