Development of a novel diagnostic method for prostate cancer that targets tumor promoting fibroblast-derived exosomes

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K09686
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56030:Urology-related
• Research Institution: Mie University
• Principal Investigator: Ishii Kenichiro 三重大学, 医学系研究科, リサーチアソシエイト (90397513)
• Co-Investigator(Kenkyū-buntansha): 佐々木 豪 三重大学, 医学部附属病院, 助教 (20644941) ; 広川 佳史 三重大学, 医学系研究科, 准教授 (30322738) ; 渡邉 昌俊 三重大学, 医学系研究科, 教授 (90273383)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 進行性前立腺がん / アンドロゲン感受性 / がん細胞分化 / がん抑制遺伝子 / NKX3-1 / がん関連線維芽細胞 / エクソソーム / マイクロRNA

Outline of Final Research Achievements

The tumor stroma of prostate cancer (PCa) contains functionally different populations of cancer-associated fibroblasts (CAFs). We hypothesize that cancer progression may be predicted by characterizing the CAFs. We investigated the effects of normal PrSC and 3 PCa patient-derived CAFs on cancer-related gene expressions in 4 human PCa sublines differing in androgen receptor (AR) dependency. The mRNA expression of tumor suppressor gene NKX3-1 in PCa cells having AR dependency was significantly increased by treatment with conditioned medium of PrSC and M5. Microarray profiling of exosomal miRNAs derived from PrSC and M5 identified miR- 449c-3p and miR-3121-3p for miRNAs related to NKX3-1 mRNA. The mRNA expression of NKX3-1 in PCa cells having AR dependency was increased by transfection of miRNA mimic (has-miR-3121-3p). These results suggest that fibroblast-derived miR-3121-3p may be a candidate of stromal morphogen for maintaining PCa cell differentiation in PCa cells having AR dependency.

Free Research Field

泌尿器科学

Academic Significance and Societal Importance of the Research Achievements

進行性前立腺がんに対するホルモン療法を開始する前に、ホルモン療法が有効な患者か、それとも抗がん剤治療を早期に始めるべきか、と判断する指標、例えば血中バイオマーカーがあれば、去勢抵抗性前立腺がんへと進展する患者数を確実に減らせる。我々が提唱する、線維芽細胞の「性質」を指標にすることができれば、ホルモン療法が効きにくく、去勢抵抗性前立腺がんへと進展し易い患者を予測し、早期に適切な治療法を判断・施行できるような前立腺がんの個別化医療実現の一歩となる。