2021 Fiscal Year Final Research Report
Role of mesenchymal stem cells in CAC development
| Project/Area Number |
19K09213
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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 | Hamamatsu University School of Medicine |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
竹内 裕也 浜松医科大学, 医学部, 教授 (20265838)
倉地 清隆 浜松医科大学, 医学部, 助教 (20397384)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Keywords | 炎症性腸疾患 / 炎症性発癌 / 間葉系幹細胞 / 線維芽細胞 |
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| Outline of Final Research Achievements |
RNA sequence analysis revealed the expression of genes involved in the improvement maintenance of the intestinal mucosa, such as BMPs and their receptors ACVR1 and downstream target genes (id1, 3), was increased, suggesting their involvement in CAC development. Therefore, we assessed the expression of BMP5 and BMP6 by immunohistochemical staining. The expression of BMP1,5,8 protein was enhanced in the stromal tissue around the crypt at dysplasia. BMPs are known to be involved in the expression of id1 and id3 via the Smad pathway. We confirmed the upregulation of id3 protein in the submucosal stromal tissue of the tumor by IHC. These results suggest that activation of the BMP-id pathway in stromal cells is involved in CAC carcinogenesis.
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| Free Research Field |
消化器外科
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| Academic Significance and Societal Importance of the Research Achievements |
癌間質には線維芽細胞の他にも免疫担当細胞や内皮細胞など様々な細胞が存在し，それらの中には間葉系幹細胞から分化したものが多く含まれている．CAC発癌は通常発癌よりも間質細胞の関与が極めて大きいと考えられているが，間質細胞の中でもっとも癌の進展に関与していると言われる間葉系幹細胞に着目した研究はこれまでにない．本研究の成果は，周囲の微小環境を標的としたCACの発癌予防の新しい治療戦略に発展する可能性がある．近年増え続ける潰瘍性大腸炎患者の予後延長につながり，その社会的意義は大きい．
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