Mechanisms for development of castration resistance by fluctuation of the differentiation in human prostate cancer cells
Project/Area Number |
16K11000
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Urology
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Research Institution | Mie University |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
白石 泰三 三重大学, 医学系研究科, 客員教授 (30162762)
広川 佳史 三重大学, 医学系研究科, 講師 (30322738)
杉村 芳樹 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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Project Period (FY) |
2016-04-01 – 2019-03-31
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Project Status |
Completed (Fiscal Year 2018)
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Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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Keywords | 去勢抵抗性前立腺癌 / ホルモン療法 / 癌細胞分化 / 線維芽細胞の多様性 / 前立腺癌患者由来線維芽細胞 / in vitro共培養実験 / 癌抑制遺伝子 / 癌遺伝子 / 前立腺癌 / アンドロゲン感受性 / 線維芽細胞 / EGF / AR-V7 / 癌細胞内シグナル伝達経路 / 癌細胞分化の揺らぎ / 細胞分化の揺らぎ / 間質リモデリング / エピジェネティック異常 |
Outline of Final Research Achievements |
In the tumor microenvironment, heterogeneous stromal component of prostate cancer (PCa) tissue contains multiple populations of fibroblasts that are associated with tumorigenesis. Fibroblasts secret a number of growth factors, cytokines, ECM proteins, and miRNAs that stimulate progression of PCa cells. In this study, we investigated the effects of fibroblasts on androgen-sensitive human PCa cell line LNCaP focusing on the expression of cancer-related genes. As for tumor suppressor genes, mRNA expression of NKX3-1 in LNCaP cells was decreased by co-culturing with fibroblasts. As for oncogenes, mRNA expressions of NFKB1 and SRC in LNCaP cells was increased by co-culturing with fibroblasts. Our data showed that mRNA expressions of cancer-related genes in LNCaP cells were highly disturbed by co-culturing with fibroblasts. The use of PCa patients-derived fibroblasts may allow us to investigate the characteristics of aggressive fibroblasts in the development of castration-resistant PCa.
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Academic Significance and Societal Importance of the Research Achievements |
進行性前立腺癌に対するホルモン療法は約4割の患者にしか効果がなく、残りの6割は初めからホルモン療法に反応しないか、最初は効果が認められるものの徐々に効果が減弱し、最終的に去勢抵抗性前立腺癌へと進展することが大きな課題である。我々は前立腺癌の去勢抵抗性獲得には癌細胞周囲に存在する線維芽細胞からのパラクライン的な刺激が重要な役割を担うと考えている。今回の結果は、進行性前立腺癌に対する治療としてホルモン療法だけでは不十分であり、癌微小環境を構成するactiveな線維芽細胞の増殖や機能を阻害することが去勢抵抗性前立腺癌への進展を抑制する有用な治療法となる可能性を示唆するものである。
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Report
(4 results)
Research Products
(34 results)
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[Presentation] Loss of fibroblasts-dependent androgen receptor activation in prostate cancer cells develops castration-resistant prostate cancer2019
Author(s)
Kenichiro Ishii, Izumi Matsuoka, Takeshi Sasaki, Manabu Kato, Kohei Nishikawa, Hideki Kanda, Yoshifumi Hirokawa, Kazuhiro Iguchi, Kiminobu Arima, Masatoshi Watanabe, Yoshiki Sugimura
Organizer
The American Association for Cancer Research (AACR) Annual Meeting 2019
Related Report
Int'l Joint Research
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[Presentation] The exploration of the order in the heterogeneity of prostate cancer-associated stroma environment2016
Author(s)
Manabu Kato, Takeshi Sasaki, Kenichiro Ishii, Manabu Miki, Kohei Nishikawa, Kiminobu Arima, Taizo Shiraishi, Neil Bhowmick, Yoshiki Sugimura
Organizer
111st American Urological Association Annual Meeting
Place of Presentation
San Diego, CA, USA
Year and Date
2016-05-06
Related Report
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