A Straightforward and Reliable Mouse Model of Colorectal Cancer by Orthotopic Transplantation

Colorectal cancer (CRC) is a major malignancy with significant global implications for human health. The development of a reliable and pathologically relevant orthotopic CRC model is essential for advancing our understanding of its molecular mechanisms and for developing more effective therapeutic interventions. However, the construction of such models is fraught with challenges primarily because of the technical complexities involved in the transplantation of CRC cells into the intestinal epithelium. In this chapter, we describe a recently developed method for generating an orthotopic CRC model within the mouse cecal epithelium. This model enables tumor development and progression within a natural tissue microenvironment and facilitates complex interactions between tumor cells and surrounding normal cells, thereby replicating the intratumor heterogeneity of CRC. All procedures in this method are visualized under stereomicroscopic observation, leading to the efficient engraftment of CRC cells and subsequent tumor development. The establishment of this reliable orthotopic CRC model, which mimics tumor development in a more natural microenvironment, offers new opportunities to explore the molecular mechanisms underlying CRC and to assess novel anticancer therapies in pathologically relevant contexts.