Dissecting molecular mechanisms underlying formation of tumor-promoting niches by colon cancer cells
| Project/Area Number |
18K08015
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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 53010:Gastroenterology-related
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| Research Institution | Juntendo University |
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Principal Investigator |
sakamoto naoto 順天堂大学, 医学部, 客員准教授 (10420845)
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| Co-Investigator(Kenkyū-buntansha) |
折茂 彰 順天堂大学, 医学(系)研究科(研究院), 教授 (70275866)
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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: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | CAFs / 大腸癌 / 癌organoid / PDXs / PDXモデル / CMS4サブタイプ / 癌オルガノイド / 患者大腸癌 / 線維芽細胞 / 中間型上皮間葉移行 / PDX / CAFｓ / 癌促進ニッチ / 癌微小環境 |
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| Outline of Final Research Achievements |
Applicants found that cancer cell lines induce TGF-b signals in normal fibroblasts and promote their differentiation into fibroblasts (CAFs), the representative stromal cells of the cancer-promoting niche. However, the factors derived from cancer cells that contributed to the formation of the CAFs niche and the characteristics of the cancer cells themselves are not clear. In the submitted study, multiple colorectal cancer patient-derived tumor xenograft (PDX) and cancer organoids were established without using a specific cancer cell line, and their ability to induce cancer-promoting CAFs was compared and examined to compare cancers. We attempted to elucidate the interaction between cells and CAFs at the molecular level.
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| Academic Significance and Societal Importance of the Research Achievements |
癌塊内にCAFsが豊富に存在すると予後不良であることが疫学的調査により報告されている。しかしながら、癌細胞の悪性度とCAFsを癌塊内にリクルートしニッチを形成する能力の相関に関して、細胞および実験動物レベルでの研究報告は乏しい。申請研究の独創性はCAFsニッチを形成する能力が癌悪性化の１つの指標であることを大腸癌PDXsや癌organoidを使用し分子レベルで明らかにすることである。
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Report
(4 results)
Research Products
(6 results)
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[Journal Article] Budesonide Foam for Ulcerative Colitis Patients Experiencing Inadequate Response to Biological Therapy.2019
Author(s)
Shibuya T, Nomura K, Okahara K, Haga K, Nomura O, Murakami T, Uchida S, Kodani T, Ishikawa D, Sakamoto N, Ogihara T, Osada T, Nagahara A.
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Journal Title
Med Sci Monit.
Volume: 25
Pages: 9855-9863
DOI
Related Report
Peer Reviewed
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[Journal Article] Molecular characterization of sessile serrated adenoma/polyps with dysplasia/carcinoma based on immunohistochemistry, next-generation sequencing, and microsatellite instability testing: a case series study.2018
Author(s)
Murakami T1,2, Akazawa Y3,4, Yatagai N3,4, Hiromoto T3,4, Sasahara N4, Saito T4, Sakamoto N3, Nagahara A3, Yao T4.
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Journal Title
Diagn Pathol
Volume: 13
Issue: 1
Pages: 88-88
DOI
Related Report
Peer Reviewed
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[Journal Article] Immunohistochemical and genetic characteristics of a colorectal mucin-rich variant of traditional serrated adenoma.2018
Author(s)
Hiromoto T1,2, Murakami T1,2, Akazawa Y1,2, Sasahara N2, Saito T2, Sakamoto N1, Mitomi H3, Nagahara A1, Yao T2
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Journal Title
Histopathology.
Volume: 73
Issue: 3
Pages: 444-453
DOI
Related Report
Peer Reviewed
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