| Project/Area Number |
17K19579
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Tumor biology and related fields
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| Research Institution | Akita University |
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Principal Investigator |
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| Project Period (FY) |
2017-06-30 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2017: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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| Keywords | 癌間質細胞 / 癌関連線維芽細胞 / CAF / Asporin / 細胞外基質 / がん間質 / 線維芽細胞 / EFEMP1 / 基質 / 胃癌 / 癌 / 細胞・組織 |
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| Outline of Final Research Achievements |
Tumors are frequently accompanied by large areas of fibrosis. Although cancer-associated fibroblasts (CAFs) are known to play pivotal roles in tumor progression, fibroblasts within tumors are comprised of heterogeneous subpopulations, and it is not clear how these heterogeneous CAFs are generated and expand in tumors. We identified a novel mechanism for expansion of CAF-like cells with inflammatory phenotypes by “Fibroblasts educate fibroblasts”, in which CAFs educated normal NFs to generate new pro-tumor fibroblasts, which we refer to as CAF-educated fibroblasts (CEFs). CEFs express inflammatory cytokines and extracellular matrix, Asporin. CEFs sequentially educate NFs one after another to further amplify cytokines and chemokines in the tumor microenvironment, which triggers cancer cell dispersion and dissemination. Further, blocking sustained CEF generation could be a suitable therapeutic target for prevention of tumor dissemination.
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| Academic Significance and Societal Importance of the Research Achievements |
腫瘍内で癌細胞をサポートする線維芽細胞の産生に関して、従来とは異なる「線維芽細胞による線維芽細胞の教育」をベースとした新規機構がある事が分かってきた。これにより産生される線維芽細胞(CEF)は、これまで大きく癌関連線維芽細胞と捉えられてきたものの中に多様性を作り、腫瘍先進部でASPNや炎症性サイトカインの増幅をもたらす。癌細胞を誘引するケモカインや、浸潤・転移を促す足場基質である事を確認したASPNを産生するCEFが常に腫瘍辺縁で自律的に広がる事は、当課題のコンセプトであるChase & Runに当てはまる。今後、CEFの産生を抑制する機構の検討から創薬への展開を目指したい。
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