How does tumor formation occur in T-cell junctions?

2022 Fiscal Year Final Research Report

• Project/Area Number: 19H03453
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 49030:Experimental pathology-related
• Research Institution: Teikyo University (2021-2022); Osaka University (2019-2020)
• Principal Investigator: Tamura Atsushi 帝京大学, 医学部, 准教授 (00362525)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: クローディン / タイトジャンクション / 胃炎 / 胃がん / 幹細胞 / invasive gland

Outline of Final Research Achievements

Tight junctions (TJs), built with the cell membrane protein called claudin (Cldn), are crucial barrier structures located between cells on the epithelial sheets of the stomach, preventing the leakage of gastric acid into the submucosa. In the stomach, gastric-type Cldn18.2 is major Cldn for TJ formation, and its deficiency in knockout (KO) mice leads to gastritis in young age and the development of gastric tumors with aging. Our results suggested that the decrease in Cldn18.2 and the consequent increase in stemness may be important in the process of gastric cancer development, based on the analysis of these mice. In this study, we further analyzed the barrier impairment and gastric inflammation in TJ-associated COBL mutant mice as similar findings.

Free Research Field

細胞生物学

Academic Significance and Societal Importance of the Research Achievements

胃がんの多くは、ヘリコバクターピロリ菌の感染と、ピロリ菌により産生されるCagA因子およびその下流シグナルによる細胞増殖や細胞極性の異常化が重要であると考えられている。クローディン欠損が、ピロリ菌感染胃炎と類似の病態を示すことから、胃がんの発生に、タイトジャンクションを介する過程が非常に重要である可能性が示唆された。今後、胃がんをはじめ、他種のがんにおいても、治療標的としてのCldnの可能性の検討が期待される。