Role of gastric microbiota on the development of gastric cacner stem-cells in H. pylori-infected gastric mucosa

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K07068
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47030:Pharmaceutical hygiene and biochemistry-related
• Research Institution: Tokai University (2021); Keio University (2019-2020)
• Principal Investigator: Tsugawa Hitoshi 東海大学, 医学部, 講師 (30468483)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: がん幹細胞 / ピロリ菌 / 胃内細菌叢

Outline of Final Research Achievements

We identified two short-chain fatty acids (SCFAs)-producing bacteria that cause CAPZA1-overexpressing cells, which are precursors to CD44v9-positive cancer stem cells. It was clarified that CD44v9-positive cancer stem cells are produced by H. pylori infection in the presence of SCFAs produced by these bacteria. In H. pylori-infected mice given drinking water containig propionic acid or butyric acid, CD44v9-positive cells were generated through overexpression of CAPZA1 in gastric mucosal epithelial cells. Our results indicate that HDAC inhibitory activity of SCFAs deregulates CAPZA1 expression, and H. pylori infection under specific SCFAs-producing bacteria enhancces the development of CD44v9-positive cancer stem cells.

Free Research Field

細菌学

Academic Significance and Societal Importance of the Research Achievements

本研究成果により、がん幹細胞の発生過程に共生細菌が関与するというこれまでに類のない全く新しいがん幹細胞発生モデルを分子生物学的に提唱でき、学術的な発展が大いに期待できる。また、本研究成果を基盤に胃内共生細菌叢への介入による胃がんの発症・再発リスク評価系や胃発がん予防・治療法の開発も期待され、今日のがん予防・治療法に革新的な変化をもたらし、臨床医学的にも期待値の大きい基礎エビデンスの提唱が実現される。