A metastatic colon cancer model using nonoperative transanal rectal injection

Abstract

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. 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. 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. 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.