GLP-1 receptor expression in cancer cells

2022 Fiscal Year Final Research Report

• Project/Area Number: 18K08532
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54040:Metabolism and endocrinology-related
• Research Institution: Juntendo University (2022); International University of Health and Welfare (2020-2021); Fukuoka University (2018-2019)
• Principal Investigator: Nomiyama Takashi 順天堂大学, 医学部, 教授 (10532559)
• Project Period (FY): 2018-04-01 – 2023-03-31
• Keywords: 糖尿病 / 前立腺癌 / GLP-1 / 細胞周期

Outline of Final Research Achievements

We examined the relationship between human prostate cancer severity and GLP-1R expression, as well as the effect of forced expression of GLP-1R using a lentiviral vector. GLP-1R expression levels were significantly inversely associated with the Gleason score of human prostate cancer tissues. Abundant GLP-1R expression and functions were confirmed in ALVA-41-GLP-1R cells. Exendin-4 significantly decreased ALVA-41-GLP-1R cell proliferation in a dose-dependent manner. DNA synthesis and G1-to-S phase transition were inhibited in ALVA-41-GLP-1R cells. SKP2 expression was decreased and p27Kip1 protein was subsequently increased in ALVA-41-GLP-1R cells treated with exendin-4. In vivo experiments performed by implanting ALVA-41-GLP-1R cells demonstrated that exendin-4 decreased prostate cancer growth by activation of GLP-1R overexpressed in ALVA41-GLP-1R cells. Forced expression of GLP-1R attenuates prostate cancer cell proliferation by inhibiting cell cycle progression in vitro and in vivo.

Free Research Field

糖尿病合併症・併存症

Academic Significance and Societal Importance of the Research Achievements

糖尿病治療の目標は患者の寿命の延長とQOLの確保にある。わが国の糖尿病患者の死因第1位が癌であることを鑑みるに、癌の発症進展を抑制する糖尿病診療を行うかが、患者の寿命を延長する糖尿病診療をするかということに言い換えることも過言ではない。しかし、糖尿病治療薬の癌に対する影響の研究は、世界的にもまだ途に就いたばかりである。本研究はGLP-1シグナルが、前立腺癌の進行抑制に作用することを確証した貴重な研究であり、ＧＬＰ－１やその受容体発現が前立腺癌の治療や予後予測の一助になる可能性を示唆した重要な研究と言える。今後臨床研究へと発展する可能性があり、また他の癌腫でも検証されることに期待が持てる。