|Budget Amount *help
¥44,070,000 (Direct Cost: ¥33,900,000、Indirect Cost: ¥10,170,000)
Fiscal Year 2021: ¥9,360,000 (Direct Cost: ¥7,200,000、Indirect Cost: ¥2,160,000)
Fiscal Year 2020: ¥11,180,000 (Direct Cost: ¥8,600,000、Indirect Cost: ¥2,580,000)
Fiscal Year 2019: ¥11,180,000 (Direct Cost: ¥8,600,000、Indirect Cost: ¥2,580,000)
Fiscal Year 2018: ¥12,350,000 (Direct Cost: ¥9,500,000、Indirect Cost: ¥2,850,000)
|Outline of Final Research Achievements
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.