| Project/Area Number |
18K07207
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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 50010:Tumor biology-related
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| Research Institution | Juntendo University |
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Principal Investigator |
Orimo Akira 順天堂大学, 医学(系)研究科(研究院), 教授 (70275866)
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| Co-Investigator(Kenkyū-buntansha) |
ワリ ナディラ 順天堂大学, 医学(系)研究科(研究院), 非常勤助教 (90751868)
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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: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | CAFs / TGF-b / Endoglin / 癌促進 / 乳癌 / 癌浸潤・転移 / CAFｓ / TGF-bシグナル / 癌微小環境 / endogln / TGF-ｂシグナル / 癌内線維芽細胞 / endoglin (CD105) |
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| Outline of Final Research Achievements |
Applicants found that cancer-associated fibroblasts (CAFs), which are abundant in the cancer microenvironment, act on nearby breast cancer cells to promote cancer malignant transformation. It has been shown that activation of stromal cell-derived factor 1 (SDF-1) and TGF-β autocrine signal is important for maintaining the phenotype of cancer-promoting CAFs. In addition, the applicants recently found that TGF-β receptor-binding protein endoglin (CD105) is highly expressed in breast cancer-derived CAFs by DNA microarray analysis. In this study, it was clarified that endoglin, which is the co-receptor of TGF-β, is highly expressed on CAFs, activates the TGF-β-Smad2/3 signal, and maintains myofibroblastic and cancer-promoting abilities. Furthermore, it was clarified that the expression of endoglin in CAFs is useful as a biomarker for predicting the prognosis of CAFs.
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| Academic Significance and Societal Importance of the Research Achievements |
申請者らは、独自に樹立した乳癌由来CAFsを使用し、対照的に非癌部より抽出された線維芽細胞との比較により、CAFsで遺伝子発現が変化している独自の遺伝子群を同定し、本研究では、endoglinに焦点を当て、CAFsでTGF-bやSDF-1オートクラインシグナルとの関与を明らかにした。また、本研究ではCAFsにおけるendoglinの発現が、患者の予後予測マーカ―になることを明確にした。さらに、CAFsにおけるendoglinの発現抑制を基に、CAFsを標的にした新規癌治療法の開発に今後役立つ可能性を見出した。
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