Abstract
Aim:Strong evidence reveals important differences between cancers in the proximal vs. distal colon. Animal models of metastatic colon cancer are available but with varying degrees of reproducibility and several important limitations. We explored whether there were regional differences in the location of murine colon cancers and assessed the utility of murine models to explore the biological basis for such differences.Methods:We re-analyzed data from our previous studies to assess the regional distribution of murine colon cancer. In survival surgery experiments, we injected HT-29 human colon cancer cells into the wall of the cecum or distal colon of Nu(NCr)-Foxn1nu or NOD.Cg-PrkdcscidIl2rgTim1Wji/SzJ mice and compared the development of primary tumors and metastases.Results:Within 7–17 weeks after intramural cecal injection of HT-29 cells, eight mice failed to develop solid primary tumors or metastases. In contrast, within four weeks after cell injection into the distal colon, 13 mice developed metastases - 12 mice developed subcutaneous metastases; of these, four developed liver metastases and one developed both liver and lung metastases. One mouse developed liver metastases only. Histological examination confirmed these lesions were adenocarcinomas.Conclusion:Our findings reveal the preferential growth of murine colon neoplasia and invasive human orthotopic xenografts in the distal mouse colon. The new approach of injecting cells into the distal colon wall results in a pattern of colon cancer development that closely mimics the progression of metastatic colon cancer in humans. This novel model of colon neoplasia has great potential for exploring anatomical differences in colon cancer and testing novel therapeutics.
Highlights
In developed countries, colorectal cancer (CRC) is the second most common cause of cancer-related death in men and the third in women[1]
Our findings reveal the preferential growth of murine colon neoplasia and invasive human orthotopic www.jcmtjournal.com
The new approach of injecting cells into the distal colon wall results in a pattern of colon cancer development that closely mimics the progression of metastatic colon cancer in humans
Summary
Colorectal cancer (CRC) is the second most common cause of cancer-related death in men and the third in women[1]. Compared to cancers of the distal colon, proximal colon cancers are more common in women, are associated with microsatellite instability and the serrated pathway, and are more likely to be at advanced stages when first diagnosed. A recent database study found that right-sided colon cancer was associated with lower cancer-specific mortality at the localization stage, equivalent mortality at the regional stage, and higher mortality at the metastatic stage[7]. Another recent retrospective study found those with left-sided colon cancer had better survival outcomes, especially with stage III cancers[10]. From 1998 to 2013, the SEER (Surveillance, Epidemiology, and End Results) database identified 90,635 and 112,679 persons diagnosed with left- and right-sided colon cancer, respectively[7]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
