Analysis of the gastric carcinogenesis with ageing based on the murine organoid model

• Project/Area Number: 18K07928
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Tohoku University
• Principal Investigator: Imatani Akira 東北大学, 医学系研究科, 教授 (30333876)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 胃オルガノイド / 加齢 / 細胞老化 / 胃発癌 / 幹細胞老化 / 胃粘膜萎縮 / ３次元細胞培養

Outline of Final Research Achievements

Ageing is one of the risk factors for gastric carcinogenesis. To clarify its mechanism with ageing, a novel 3D cell culture system “Organoids” established from the normal mice gastric mucosa was employed in this study. Interestingly, several gastric organoids with accelerated cell proliferation emerged from the gastric mucosa of the aged mice. The cell proliferation depended on Wnt/beta-catenin signaling and was involved in the suppressed expression of cellular senescence-related genes. This study suggested that the evasion from cellular senescence leads the gastric carcinogenesis with ageing.

Academic Significance and Societal Importance of the Research Achievements

本研究の加齢マウス由来の胃オルガノイドを用いた検討から、胃粘膜組織では、加齢とともに生理的な幹細胞老化から逸脱して、細胞増殖能が高い病的幹細胞（クローン）が出現することが類推でき、加齢に伴って胃癌が発生する極めて初期の病態の一端と考えられた。超高齢社会を迎えている日本において、胃癌に対する分子生物学的診断や治療の必要性について考える上で、本研究は基礎的資料となると思われた。