A metastatic colon cancer model using nonoperative transanal rectal injection.

BACKGROUND: This study aimed to develop a noninvasive orthotopic model for metastasis of colon and rectal cancer using a transanal approach. Currently, the most accurate orthotopic representation of metastatic human colon cancer is via a cecal injection. The transanal model allows for further examination of systemic immune responses, tumor take, and onset of metastasis without prior surgical intervention. METHODS: For this study, 60 Balb/c mice were anesthetized and subjected to gentle anal dilation using blunt-tipped forceps at the anal opening. Murine colon cancer parental CT26 or luciferase-labeled CT26 (CT26-luc) cells were injected submucosally into the distal posterior rectum (30 CT26 and 30 CT26 injections) at concentrations of 2.5 x 10(4), 1 x 10(5), and 1 x 10(6) in a volume of 50 microl. Tumor growth and metastatic development was monitored at 5-day intervals for 50 days. All the remaining mice were killed on postinjection day 50. RESULTS: The optimal concentration for metastasis and survival of the mice was 2.5 x 10(4) cells. Higher concentrations of cells yielded higher mortality but did not result in metastasis. The overall success of tumor growth in both experiments using the transanal rectal injection was 65%. Histology showed that all tumors were poorly differentiated adenocarcinomas. Two mice (3.3%) from the 2.5 x 10(4) CT26-luc group showed metastatic colonic adenocarcinoma to the liver on postinjection day 50. CONCLUSION: Transanal rectal injection of colon cancer cells offers a nonoperative orthotopic murine model for colon cancer that may lead to the development of metastasis. By using an orthotopic model, more aspects of metastatic colon cancer can be evaluated without the influence of a previous abdominal incision. These results warrant more investigation.

Novel murine model for colon cancer: non-operative trans-anal rectal injection.

BACKGROUND: This study was conducted to develop a modified murine model of colon cancer that is non-operative. Currently, the most accurate orthotopic murine model of colon cancer requires an invasive procedure involving cecal injection of colon cancer cells and therefore limits the ability to perform immunological studies subsequent to cecal resections. MATERIALS AND METHODS: Murine colon cancer (CT26) cells were injected submucosally into the distal, posterior rectum of BALB/c mice. Care was taken not to pass transmurally into the pelvic cavity. Different magnifications (10x versus 100x) were used for injection, and primary tumor growth and metastatic disease were studied. RESULTS: In the initial study, 3/7 mice injected using 10x magnifications had notable, large tumor originating from the rectal wall, and histology revealed that all excised tumors were poorly differentiated adenocarcinoma. In the second study, 8/10 mice injected using 100x magnifications had notable tumor originating from the rectal well, and 4/8 mice had abnormal lung tissue with pathological evidence of hemorrhagic pulmonary edema. The use of 10x magnification resulted in 43% tumor take. In sharp contrast, 80% tumor take was observed with 100x magnification. The overall success of tumor take was 65% using the trans-anal rectal injection model. CONCLUSIONS: Our modified orthotopic murine model of colon cancer offers an alternative non-operative murine model for colon cancer and is less invasive than the traditional orthotopic model (i.e., cecal injection). This model may allow for more accurate investigations of inflammation and immune responses to surgical intervention without the influence of previous abdominal surgery.