Development of in vitro assay system for carcinogenesis using iPS-derived intestinal epithelial stem cells

2015 Fiscal Year Final Research Report

• Project/Area Number: 26640089
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Tumor biology
• Research Institution: National Cancer Center Japan
• Principal Investigator: Mutoh Michihiro 国立研究開発法人国立がん研究センター, 社会と健康研究センター, 室長 (30392335)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Keywords: 大腸がん / iPS / 放射線照射 / 上皮間葉変換

Outline of Final Research Achievements

<Aim> The processes of carcinogenesis are so complex that they are difficult to reproduce in a cell system. However, establishment of a simple model may accelerate our knowledge of carcinogenetic processes. In the present study, we tried to reproduce carcinogenetic processes by the induction of stochastic changes in vitro. <Methods & Results> We first obtained stem cells from the lower digestive tract derived from iPS cells. The maintenance medium allowed us to culture the cells for more than a half-year without any neoplastic feature changes. We next tried to induce somatic mutation by treating 53-passage-cells with 5 Gy radiation. Five months later, the cells were obviously changed in shape to spindle formation. The molecular markers of differentiation and intestinal epithelium were down-regulated, and we obtained epithelial-mesenchymal transformed cells. <Future plan> We are now evaluating the neoplastic characters using a xenograft model.

Free Research Field

がん予防学