A New Murine Model For Colon Cancer Using Non-Operative Transanal Rectal Injection

2941 Background: Currently, the most accurate orthotopic representation of human colon cancer is a cecal injection. However this requires a surgical incision and therefore limits the ability to accurately measure immune responses to any subsequent colon resections. Therefore, in order to study the immunological response following large bowel resection on mice with colon cancer, the traditional cecal injection model must be modified. In this study we designed an alternative orthotopic model for primary colon cancer by using a trans-anal approach. Methods: Anesthetized Balb/c mice were injected with 25,000 murine colon cancer CT26 cells using a 30-gauge syringe, submucosally into the distal, posterior rectum. Care was taken not to pass transmurally into the pelvic cavity. Seven mice were injected using operating loupes with 10x magnification and sacrificed on post-injection day 17. An additional 10 mice were injected using 100 x magnifications and sacrificed on day 20. The rectum, rectal wall and lungs were photographed, measured, and processed for histology and reviewed by a pathologist. Results: Three of seven mice in the initial study had notable, large tumor originating from the rectal wall, all showing poorly differentiated adenocarcinoma. In the second group, eight out of ten mice had gross tumor originating from the rectal wall. Four of these mice had abnormal lung tissue, suggesting metastasis. Slides from the second group of mice are under review. A 10x magnification resulted in a 43% tumor growth. In contrast and an 80% tumor growth rate was observed with 100x magnification. The overall success rate of tumor growth was 65% using the trans-anal, submucosal tumor injection model. Conclusion: Trans-anal injection of colon cancer cells offers an alternative non-operative orthotopic murine model for colon cancer. By using an orthotopic model that does not require abdominal surgery for implantation, more aspects of inflammation and immune response can be evaluated without the influence of a previous abdominal surgery.