Development of a Reliable Colorectal Cancer Liver Metastasis Model

Abstract

The liver is the most frequent and most fatal site of distant spread of colorectal cancer. Most current animal models of liver metastases utilize direct liver or intravascular injection (dissimilar to mechanisms of metastasis) or immunosuppression to establish metastases.Aim:The aim of this study was to develop a reliable rat model of liver metastases in immunocompetent hosts, whereby metastases spread hematogenously as in colorectal cancer.Methods:WB-2054 is a poorly differentiated colon adenocarcinoma induced by 1,2 DMH in a WF × BN F1hybrid rat. WB-2054-M0, M1, M2, M3, and M4are successive metastatic variant cell lines obtained through serial application of the Fidler hypothesis. WF × BN F1rats were inoculated intrasplenically with 1 × 106(M0) or 5 × 106(M0–M4) cells; the spleen was left intact. Animals were evaluated 4 to 12 weeks postinjection and, if no metastases were found, reexplored 1–2 weeks later. Animals with liver metastases were sacrificed, and full abdominal and thoracic zoopsy was performed. Livers were excised and serially sectioned, to determine size, number, and location of liver metastases, and studied histologically to confirm the nature of the metastases.Results:44% (4/9), 80% (8/10), 86% (65/76), 94% (34/36), and 100% (65/65) of animals inoculated with the M0, M1, M2, M3, and M4cell lines, respectively, developed liver metastases. Metastases were uniformly spread throughout all lobes of the livers.Conclusion:We have developed an extremely hepatotrophic metastatic colorectal cancer cell line. Intrasplenic injection of WB-2054-M4cells is a reliable model for producing colorectal cancer liver metastaseswithoutthe need for immunosuppression and should prove valuable in colorectal liver metastasis experiments.