Investigation of the gastric carcinogenesis using gastric tumor organoid library and artifitial cancer organoids.

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K15967
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Gastroenterology
• Research Institution: Keio University
• Principal Investigator: Nanki Kosaku 慶應義塾大学, 医学部(信濃町), 助教 (30571137)
• Project Period (FY): 2017-04-01 – 2019-03-31
• Keywords: 胃がん / オルガノイド

Outline of Final Research Achievements

In this study, we constructed a stomach tumor organoid library using organoid culture technology, and compare its phenotype with each result of molecular genetic analyses. Transformation of its morphology and niche requirement were caused by various genome and epigenomic changes, and it was found that CDH1 and TP53 co-mutations caused autonomous growth in gastric cancer, CDH1 and TP53 mutations cause autonomous growth. For verification, we established CDH1/TP53 co-mutated engineered gastric organoids. The engineered organoids could grow autonomously. Furthermore, we imploved the efficiency of the success rate of xeno-transplantation of gastric cancer organoids to immuno-deficient mice by co-transplantation with fibroblasts.
It can be expected to lead to a new treatment for gastric cancer.

Free Research Field

消化器内科学

Academic Significance and Societal Importance of the Research Achievements

本研究で構築した胃がんオルガノイドライブラリーは、これまでのin vitro研究で主に使用されてきた細胞株に比して、より臨床胃がんに近い特性を持ち、そのためがん研究の非常に有用なツールとなりうる。
また、本研究で用いられた、ヒト胃がんオルガノイドを培養上の形質で分類し、それぞれの分類において見出した分子遺伝学的特性を正常上皮に再現し検証した方法は、これまでにない新規の研究手法であり、他のがん腫や消化器疾患の研究進捗に非常に有用であると考えられる。