The intraportal injection model: A practical animal model for hepatic metastases and tumor cell dissemination in human colon cancer

Background: The development of new therapeutic strategies for treatment of metastasized colorectal carcinoma requires biologically relevant and adequate animal models that generate both reproducible metastasis and the dissemination of tumor cells in the form of so-called minimal residual disease (MRD), an expression of the systemic character of neoplastic disease. Methods: We injected immunoincompetent nude mice intraportally with different numbers (1 x 10(5), 1 x 10(6) and 5 x 10(6) cells) of the human colon carcinoma cell lines HT-29 and SW-620 and investigated by histological studies and CK-20 RT-PCR the occurrence of hematogenous metastases and the dissemination of human tumor cells in bone marrow. Results: Only the injection of 1 x 10(6) cells of each colon carcinoma cell line produced acceptable perioperative mortality with reproducible induction of hepatic metastases in up to 89% of all animals. The injection of 1 x 10(6) cells also generated tumor cell dissemination in the bone marrow in up to 63% of animals with hepatic metastases. Conclusion: The present intraportal injection model in immunoincompetent nude mice represents a biologically relevant and adequate animal model for the induction of both reproducible hepatic metastasis and tumor cell dissemination in the bone marrow as a sign of MRD.