Mechanism of heterogeneity-induced colon cancer malignant progression
Description: In this project, we have examined the role of genetic heterogeneity in malignant progression of intestinal tumors. For this purpose, we have constructed genetically engineered mouse models and tumor-derived organoid transplantation models. By comprehensive histological analysis, we have successfully linked specific combinations of driver mutations to each process of malignant progression, such as submucosal invasion, intravasation, and metastasis. Moreover, we found that malignant metastatic tumor cells induce fibrotic niche generation in the liver by activation of hepatic stellate cells, and non-metastatic cells survive and proliferate in the fibrotic microenvironment, which leads to development of polyclonal metastasis. These results suggest that targeting fibrotic niche generation in the liver will be a possible preventive and therapeutic strategy against colon cancer metastasis.
Amount: ¥44,070,000
Funding type: research
Funder scheme: Grant-in-Aid for Scientific Research (A)
Start date: 2018-04-01
End date: 2022-03-31
Investigator: Masanobu OSHIMA
Institution: Kanazawa University
Funded outputs count: 12
Funder award ID: 18H04030
OpenAlex ID: G4543283277