A syngeneic orthotopic mouse model of metastatic colorectal cancer

Colorectal cancer (CRC) development is initiated in the colon-rectum sections of the gut, by the emergence of a primary tumor. CRC slowly progresses to a multiple locations metastatic disease, involving secondary tumors arising in various organs, such as the liver. Mouse models have been developed to investigate the immune response, locally generated in primary tumors. Classically, tumors are implanted under the skin, for practical reasons and simplicity of monitoring. However, the skin location does not necessarily recapitulate the tumor immune microenvironment (TME) that would normally be generated in the gut. The orthotopic CRC mouse model, that we describe hereafter, was generated to investigate the colon-local mechanisms driving the establishment and the polarization of primary tumors TME. In this chapter, we detail the procedures used to implant syngeneic colon tumor cells in the cecum of immunocompetent mice and to monitor the progression of visceral tumors in live mice. The same procedure can be implemented using other tumor cell lines and mouse genetic backgrounds.