Development of a novel mouse model of gastric cancer and elucidation of the molecular mechanisms that induce the intestinal-type to diffuse-type transition.

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K20836
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0901:Oncology and related fields
• Research Institution: Fujita Health University (2023); Keio University (2022)
• Principal Investigator: Yamasaki Juntaro 藤田医科大学, がん医療研究センター, 研究員 (10963580)
• Project Period (FY): 2022-08-31 – 2024-03-31
• Keywords: 胃がん

Outline of Final Research Achievements

This study established a novel diffuse-type gastric cancer mouse cell line by knocking out Cdh1, which frequently mutates in diffuse-type gastric cancer, in the mouse gastric cancer cell line GAN-KP that forms intestinal-type gastric cancer. A mouse model using the Cdh1-knockout gastric cancer cells (GAN-KPC) was created, and comparisons with the original intestinal-type gastric cancer cells (GAN-KP) suggested that the knockout of Cdh1 promotes invasion and metastasis. Additionally, the study evaluated the differences in sensitivity to major anticancer drugs and metabolic characteristics, indicating that the knockout of Cdh1 contributes to an increased dependence on glycolysis and a decrease in ferroptosis sensitivity.

Free Research Field

胃がん

Academic Significance and Societal Importance of the Research Achievements

胃がんの組織型は大きく分けてIntestinal-type (腸型)、Diffuse-type (びまん型)、両者が混在するMixed-type (混合型)が存在し、中でも細胞の未分化性が高く頻繁に腹膜播種を引き起こすDiffuse-typeは、とくに予後不良になることが知られている。本研究で新たに樹立されたびまん型胃がんマウスモデルは免疫が正常な同系マウスに同所移植されたもので、免疫細胞や腫瘍微小環境との相互作用を明らかにするための有用なモデルであり、びまん型胃がんの好転移性メカニズムの解明や治療標的の探索に用いることで、予後不良なびまん型胃がんに対する新たな治療薬の開発に貢献しうる。