Mechanisms of prostate cancer heterogeneity induced by disease-associated reprogramming

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K10583
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Urology
• Research Institution: Mie University
• Principal Investigator: Arima Kiminobu 三重大学, 医学系研究科, 准教授 (10175995)
• Co-Investigator(Kenkyū-buntansha): 佐々木 豪 三重大学, 医学部附属病院, 助教 (20644941) ; 白石 泰三 三重大学, 医学系研究科, 客員教授 (30162762) ; 石井 健一朗 三重大学, 医学系研究科, 助教 (90397513) ; 加藤 学 三重大学, 医学部附属病院, 助教 (60626117)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 前立腺 / 疾患関連リプログラミング / 間質リモデリング / 線維芽細胞の多様性 / 前立腺癌患者由来線維芽細胞 / 前立腺幹・前駆細胞 / in vitro共培養実験 / in vivo共移植実験

Outline of Final Research Achievements

Deregulation of epithelial-stromal interactions is considered to play a critical role in the initiation of prostate cancer (PCa). Fibroblasts secret a number of growth factors, cytokines, and miRNAs that affect cellular differentiation of epithelial cells. In this study, we investigated the effects of fibroblasts on the expression of tumor suppressor genes in non-transformed human prostatic epithelial cell line BPH-1 in vitro and in vivo. In in vitro co-culture experiments, mRNA expression of GSTP1 in BPH-1 cells was decreased by co-culturing with fibroblasts. In in vivo co-inoculation experiments, mRNA expression of GSTP1 was quite low in infiltrating solid branching epithelial cords surrounding tenascin-C-expressing fibroblasts. Our data showed that GSTP1 in BPH-1 cells were highly disturbed by interactions with fibroblasts. The use of PCa patients-derived fibroblasts may allow us to investigate the characteristics of aggressive fibroblasts in the initiation of PCa.

Free Research Field

泌尿器科学