Elucidation of high-fat diet-inbduced inflammation and application to treatment for prostate cancer

2022 Fiscal Year Final Research Report

• Project/Area Number: 18K16693
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56030:Urology-related
• Research Institution: Osaka University
• Principal Investigator: Hayashi Takuji 大阪大学, 大学院医学系研究科, 招へい教員 (50747079)
• Project Period (FY): 2021-03-01 – 2023-03-31
• Keywords: 前立腺癌 / 免疫細胞 / 炎症反応 / 腸内細菌叢 / 高脂肪食 / 肥満 / モデルマウス

Outline of Final Research Achievements

High-fat diet (HFD) induced local inflammation and accelerated tumor growth via IL6/pSTAT3 pathway in autochthonous genetically-engineered model mice which corresponds to somatic mutations of human prostate cancer. These phenomena were accompanied with the macrophage polarization and the increase of myeloid-derived suppressor cells (MDSCs) in prostate cancer. In human, tumor-infiltrating MDSCs were increased in obese patients with prostate cancer. Both celecoxib, one of non-steroidal anti-inflammatory drugs, and metformin inhibited these inflammatory responses and tumor growth in the model mice.
Intestinal bacteria, acting through short-chain fatty acids, regulate systemic and local prostate IGF1 in the host, which can promote proliferation of prostate cancer cells. HFD promotes prostate cancer growth through histamine signaling via mast cells. HFD-induced gut dysbiosis might be involved in the inflammatory cancer growth.

Free Research Field

前立腺癌と炎症反応および免疫細胞との関連

Academic Significance and Societal Importance of the Research Achievements

肥満前立腺癌患者における免疫細胞を介した前立腺癌増殖のメカニズムが明らかとなり、局所でのIL6シグナルは前立腺癌治療のターゲットとなり得ることが示唆された。
また腸内細菌叢の変化および肥満細胞でのヒスタミンシグナルが高脂肪食による前立腺癌増殖の促進に関与していることがわかり、食事・免疫細胞・前立腺癌との相互作用の解明を進めることによって、前立腺癌の発症予防や増殖抑制による新規治療法の開発に大きく寄与できると考えられた。