Project 462134

Colon cancer is one of the most common and deadly cancers in Canada. Approximately, one in 13-16 people in Canada is expected to develop colon cancer during their lifetime, and more than 20 people die from it every day. Treatment options are largely limited to surgery and chemo/radiation therapies, which often entail recurrence and secondary complications. The tumor microenvironment is the region that immediately surrounds a tumor, which includes fibroblasts, immune cells and other stromal cell types. Producing key signaling molecules and the extracellular matrix that promotes tumor growth and survival, it is a constant influence on tumor progression. However, the specific cellular identity of this microenvironment in intestinal cancer is still unclear. Stem cells give rise to functional cell types required for gut function. Notably, we and others have demonstrated that several stromal cell types in close proximity to stem cells produces key signals for normal gut function. Interestingly, these stromal cells increase in number, surrounding the tumors, implying their dysregulation in cancer. However, their cell type-specific roles in gut tumor development are still unclear. Utilizing novel mouse models targeting these cells in combination with cancer models, we will not only determine the cell type-specific roles of gut stromal cells in cancer but also define the underlying cellular mechanisms. This work will form a key foundation for the development of novel approaches targeting gut stromal cells in cancer.