Lifestyle-induced metabolite profile changes regulate prostate cancer growth

2024 Fiscal Year Final Research Report

• Project/Area Number: 22K09447
• 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: Osaka University
• Principal Investigator: Hatano Koji 大阪大学, 大学院医学系研究科, 講師 (60762234)
• Co-Investigator(Kenkyū-buntansha): 藤田 和利 近畿大学, 医学部, 教授 (50636181)
• Project Period (FY): 2022-04-01 – 2025-03-31
• Keywords: 前立腺癌 / 生活習慣 / メタボローム / 運動 / 発癌

Outline of Final Research Achievements

In addition to genetic predisposition, lifestyle plays a major role in the development and progression of prostate cancer. Epidemiological studies have identified obesity and a high-fat diet as factors that promote prostate cancer, and exercise as a factor that can be protective. We have been investigating the mechanism of lifestyle-induced prostate cancer growth using prostate cancer mice model with prostate-specific knockout of the Pten gene. In this study, we focused on metabolite profiles in tumors. We found that the One-Carbon pathway was activated in mice fed a high-fat diet, which promotes prostate cancer growth. On the other hand, when the mice were given an exercise intervention, they showed a reduction in prostate cancer and Ki-67 positivity. Exercise significantly altered arginine metabolism in tumors. The results of this study reveal a mechanism for the regulation of prostate cancer growth via lifestyle-induced changes in metabolite profiles.

Free Research Field

泌尿器科学

Academic Significance and Societal Importance of the Research Achievements

本邦では人口の高齢化が進んでおり、前立腺癌の罹患数および死亡数の増加が社会的な問題となっている。科学的根拠に基づくがん予防法を確立できれば、多くの人が健康長寿を享受できる社会作りにつながる。疫学研究から、前立腺癌の発がんと進展には遺伝的素因に加えて生活習慣が大きく関与することが示された。高脂肪食を特徴とする欧米型の食生活や肥満は前立腺癌の進展につながる。一方、運動は前立腺癌の死亡リスクを低下させるが、そのメカニズムは未解明である。本研究では、生活習慣による代謝物プロファイル変化を介する前立腺癌の増殖制御メカニズムを明らかにした。本研究の成果は、新たな前立腺がん予防法の確立に向けた基盤となる。