2019 Fiscal Year Final Research Report
Development of stromal differentiation therapy focusing on stability of prostatic outgrowth
| Project/Area Number |
17K11130
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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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| Research Field |
Urology
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| Research Institution | Mie University |
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Principal Investigator |
Sugimura Yoshiki 三重大学, 医学系研究科, リサーチアソシエイト (90179151)
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| Co-Investigator(Kenkyū-buntansha) |
加藤 学 三重大学, 医学系研究科, 助教 (60626117)
石井 健一朗 三重大学, 医学系研究科, 助教 (90397513)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Keywords | 前立腺 / 増殖機構 / 間質分化誘導 / ソニック・ヘッジホッグ / 無血清器官培養実験法 / 去勢条件 / 基底上皮細胞 / 間質リモデリング |
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| Outline of Final Research Achievements |
A decrease in the androgen level has shown to induce stromal remodeling and subsequent aberrant activation of FGF2/FGFR signaling in the mouse prostate. Thus, we hypothesize that improvement of androgen deprivation therapy-induced stromal remodeling may suppress the stromal growth signals to prostate cancer cells. In this study, we focused on the role of sonic hedgehog (Shh) in the mouse prostate structure. The number of tenascin-C (TNC)-positive fibroblasts and basal epithelial cells was increased in the absence of androgen. The number of TNC-positive fibroblasts was clearly decreased by Shh/Smo agonist SAG treatment, whereas that of basal epithelial cells was not changed. No response to Shh signaling pathway inhibitor cyclopamine and purified Shh was observed in the increased number of basal epithelial cells. These results suggest that improvement of prostate stromal structure by Shh activation may not suppress the proliferation of basal epithelial cells in the absence of androgen.
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| Free Research Field |
泌尿器科学
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| Academic Significance and Societal Importance of the Research Achievements |
癌治療をはじめ、病気に対する治療では「増殖するものを阻害する」ことが多い。しかし、病気の成り立ちを考えると、元々は正常な細胞群が組織を構築し、安定的に機能することで生体は恒常性を維持する。そこで、我々は前立腺の異常増殖性病変部で観察される線維芽細胞が優位でactiveな環境を平滑筋細胞が優位でinactiveな環境へと変化させることで前立腺増殖機構が安定化し、異常増殖性病変の発生や進展を抑制すると考えた。マウス前立腺を用いた検討では、アンドロゲン非存在下でもShhシグナルを活性化させれば間質リモデリングが改善されるものの、基底上皮細胞数を増加させる増殖シグナルの抑制には至らないことが判明した。
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