Tumor Cell Dissemination in a Human Colon Cancer Animal Model: Orthotopic Implantation or Intraportal Injection?

Abstract

Background: The development of therapeutic strategies for treatment of metastasized colorectal carcinoma requires biologically relevant and adequate animal models generating both metastases and the dissemination of tumor cells. Methods: To prove the efficiency of orthotopic implantation concerning induction of minimal residual disease (MRD) colorectal cancer tissue from 10 patients was transplanted orthotopically into nude mice. In the intraportal injection model 1 × 10⁶ HT-29 human colon cancer cells were injected. We investigated by histological studies and CK-20 RT-PCR the occurrence of hematogenous metastases and the dissemination of human colon cancer cells in bone marrow. Results: Following orthotopic implantation of human colon cancer tissue the lymph node and hepatic metastasis rates were low. MRD as reflected by CK-20 positivity of the bone marrow was present in 22.2%. The intraportal injection of 1 × 10⁶ HT-29 human colon cancer cells produced hepatic metastases in up to 89% of all animals. The intraportal injection of 1 × 10⁶ cells also generated MRD in the bone marrow in 63% of animals. Conclusions: The intraportal injection model represents a biologically relevant and adequate animal model for the induction of both reproducible hepatic metastasis and MRD in the bone marrow. In this regard it seems to be superior to the orthotopic implantation model.