Developing mouse models of inflammation-driven invasive gastric cancer to reveal novel therapeutic targets

2019 Fiscal Year Final Research Report

• Project/Area Number: 17H01399
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Tumor biology
• Research Institution: Kanazawa University
• Principal Investigator: Barker Nicholas 金沢大学, その他部局等, リサーチ・プロフェッサー (30787651)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: Gastric cancer / Mouse model / Inflammation / Lgr5 / Organoid

Outline of Final Research Achievements

There is an urgent, unmet need for accurate mouse models of invasive, metastatic gastric cancer that can be used to derive important mechanistic insight into gastric cancer progression and to identify candidate cancer stem cell populations as novel therapeutic targets. We generated the first inflammation-driven mouse models of invasive gastric cancer for use in studying gastric cancer development in the stomach, with a particular focus on understanding the role of Lgr5+ stem cells and Lgr5+ cancer stem cells in this process.
These mouse models will also be invaluable as screening modalities for accurately evaluating the efficacy/selectivity of future anti-cancer therapeutics. The mouse models and experimental procedures detailed here are original and will deliver results that are expected to have a major impact on the gastric cancer research field.

Free Research Field

幹細胞生物学

Academic Significance and Societal Importance of the Research Achievements

胃がんの発生機序に対する私たち理解は限られており、このことが効果的な治療法の開発を妨げている。我々は、炎症を伴って発生するヒト胃がんを模倣する新たな胃がんマウスモデルを樹立し、生体内・生体外の解析を通してLgr5遺伝子を発現する胃がん細胞が、がん幹細胞である可能性を示唆する結果を得た。また、胃がんの悪性化に寄与する新たなドライバー変異を持つマウスモデルを作製し、それらの遺伝子変異が胃がんの進展に与える影響を解析した。これらの研究手法や得られた結果は、胃がんの進行を制御するメカニズムの迅速な解明や胃がんに対する新たな治療法の開発につながることが期待される。