Animal models of colorectal cancer

Abstract

Colorectal cancer is a heterogeneous disease that afflicts a large number of people in the United States. The use of animal models has the potential to increase our understanding of carcinogenesis, tumor biology, and the impact of specific molecular events on colon biology. In addition, animal models with features of specific human colorectal cancers can be used to test strategies for cancer prevention and treatment. In this review we provide an overview of the mechanisms driving human cancer, we discuss the approaches one can take to model colon cancer in animals, and we describe a number of specific animal models that have been developed for the study of colon cancer. We believe that there are many valuable animal models to study various aspects of human colorectal cancer. However, opportunities for improving upon these models exist.

Oncogenic Kras drives invasion and maintains metastases in colorectal cancer

“…1B;Fearon and Vogelstein 1990). In our model, the use of the colon-restricted 4-OHT enema produced tumors that arose primarily in the colon (85% of all gastorintestinal tumors) (Table 1), which is in contrast to the preponderance of small intestine tumors observed in most extant models (Moser et al 1990;Johnson and Fleet 2013;Chanrion et al 2014;Dow et al 2015). Detailed histopathological staging was performed to document the occurrence of T1 (invasion through the muscularis mucosa), T2 (invasion into the muscularis propria), T3 (invasion into the subserosa), and T4 (invasion through the serosa and outer intestinal wall) stage tumors.…”

Iron Uptake via DMT1 Integrates Cell Cycle with JAK-STAT3 Signaling to Promote Colorectal Tumorigenesis

“…Patients with lower iron or in mouse models treated with low iron diet exhibit a decrease in CRC (Ashmore et al, 2015; Bastide et al, 2015; Nelson, 2001). The majority of previously described mouse genetic models of intestinal tumorigenesis mainly develop small intestinal adenoma (Johnson and Fleet, 2013). The small intestine and colon vastly differ with respects to the relative levels of luminal iron (Blachier et al, 2007).…”

Generation of an inducible colon-specific Cre enzyme mouse line for colon cancer research

“…Controlled in vivo studies in genetic mouse models based on the Cre-loxP system offer an important avenue to model the molecular etiology of CRC development via timed mutation of oncogenes and tumor suppressor genes, allowing testing of potential preventive and therapeutic interventions (10,11). A preferred mouse model for CRC should involve Cre expression specifically in colonic epithelial cells to closely mimic the disease development observed in humans.…”