Regulation of pancreatic cancer progression by targeting Hic-5, a TGF-beta-inducible adaptor expressed in cancer-stroma.
| Project/Area Number |
19K08404
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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 | Showa University |
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Principal Investigator |
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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: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
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| Keywords | 膵がん / 膵線維化 / がん微小環境 / がん関連線維芽細胞 / 微小環境制御 / Hic-5 / TGF-b / 細胞接着班分子 |
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| Outline of Research at the Start |
がん間質はがん細胞増殖作用を持ち、発がん・がん進展に重要な役割を持つことが認識されている。申請者らは近年、活性酸素応答性アダプター分子 Hic-5 ががん間質にのみ高発現し細胞外マトリックス (ECM)を制御していること、および自作した Hic-5 欠損マウスで大腸がんの発症がほぼ完全に抑制されることを報告した。本研究では間質の豊富な膵がん発症へのHic-5 の関与を明らかにすると共に、がん組織の硬い ECM 構造の実態解析に着手する。最終的に既存抗がん剤とは異なる難治性がんの間質機能抑制という新しい作用機序を持つ新規がん治療ターゲット分子の提唱を目指す。
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| Outline of Final Research Achievements |
Alteration in the density of extracellular matrix (ECM) occurs in the tumor stroma. We have previously demonstrated that Hydrogen peroxide-inducible clone-5 (Hic-5) was strongly induced in CAFs found in human colorectal cancer and responsible for generating a tumor-promoting stroma. In this study, we focused on pancreatic cancer which is characterized by a dense stromal response, and investigated the contribution of Hic-5 to pancreatic cancer development through regulation of cancer stromal phenotype using a mouse model of pancreatic cancer. Furthermore, we clarified the involvement of Hic-5 in pancreatic fibrosis, which is considered to be one of the causes of pancreatic cancer resistance to treatment.
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| Academic Significance and Societal Importance of the Research Achievements |
膵線維化は難治癌である膵がんの治療抵抗性の一因と考えられており、本研究により膵線維化制御メカニズムの一因が明らかにされた。がん組織中の線維化を標的とした新たな膵がんの治療戦略開発につながるデータである。
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Report
(4 results)
Research Products
(11 results)
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[Journal Article] Light-at-night exposure affects brain development through pineal allopregnanolone-dependent mechanisms2019
Author(s)
Haraguchi S, Kamata M, Tokita T, Tashiro KI, Sato M, Nozaki M, Okamoto-Katsuyama M, Shimizu I, Han G, Chowdhury VS, Lei XF, Miyazaki T, Kim-Kaneyama JR, Nakamachi T, Matsuda K, Ohtaki H, Tokumoto T, Tachibana T, Miyazaki A, Tsutsui K.
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DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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