Development of an Orthotopic Colorectal Cancer Mouse Model for Radiation Therapy Studies

Abstract

Abstract Radiation is commonly used before surgery to reduce tumor burden in rectal cancer. It has been suggested that radiation therapy induces an immune response against the tumor. Previous work using mice ectopic models has shown a correlation between tumor regression and the production of IFN-g and the induction of cytotoxic T cells after radiotherapy. Ectopic models, such as the use of colon cell lines in leg muscle, provide us with some information about the response to radiation, but this response may differ if the tumor is grown orthotopically in the tissue from which it originates. To assess this difference in response, we have developed an orthotopic model to study the growth of colorectal cancer in mice and the response to radiation treatment. In our model, MC38 adenocarcinoma murine cells expressing luciferase are implanted in the rectal wall of C57BL/6 mice through the serous membrane. Tumor growth, assessed using IVIS, revealed tumor masses that steadily increase in size reaching approximately 1 gram 21 days post-injection of 50,000 cells. Importantly, tumor growth in most mice was limited to the site of injection, as mesenteric and omental sites were free of tumor burden. The cellular composition and the morphology of these tumors is being examined using flow cytometry and immunohistochemistry, respectively. Furthermore, studies are underway to determine the response of these tumors to fractionated radiation and to determine if there are differences from the ectopic models of colon cancer. This more clinically relevant model will improve our understanding of response to radiotherapy in colorectal cancer and help develop more effective treatments for this disease.