Cancer Research Institute of Kanazawa University

　The genome analyses identified driver genes for gastric and colorectal cancer. We have constructed novel mouse models and tumor-derived organoid transplantation models to examine the mechanisms of development and metastasis of gastrointestinal cancers.

【Polyclonal metastasis of intestinal tumor cells】

　In the concept of polyclonal metastasis, cell clusters are detached from the primary site and develops genetically heterogenous metastatic lesions. Using the mouse intestinal tumor-derived organoids, we found that malignant metastatic cells can generate fibrotic niche in the liver, which support survival and proliferation of non-metastatic cells within the same clusters and develop polyclonal metastasis (Kok SY, Oshima H, et al, Nat Commun, 2021).

【Nano-scale mapping of genotype-defined cancer cells】

　Using the high speed (HS)-scanning ion conductance microscope (SICM), we have analyzed cell surface topography and physical properties including stiffness of intestinal tumor-derived organoids, and identified metastatic cell-specific mechanical characteristics (Wang D, et al, Biomaterials, 2022).

【Cancer evolution by negative selection mechanism】

　AKTP organoids carrying four driver mutations in Apc, Kras, Tgfbr2 and Trp53 were established from metastatic intestinal tumors. We found that about 30% of AKTP cells lost metastatic ability and eliminated from the tumor population by negative selection. Thus, it is possible that cancer evolution is promoted by both positive and negative selections (Morita A, et al, Cancer Sci, 202).