Quantitative detection of lac-Z-transfected CC531 colon carcinoma cells in an orthotopic rat liver metastasis model

Disseminated colon carcinoma metastases in the liver are associated with low cure rates and constitute a serious therapeutic problem. Appropriate experimental models which mimic metastases development and outgrowth can provide insight into the mechanism of this lethal process and facilitate the finding of new approaches for its control. We established an orthotopic liver metastases model based on CC531 rat colon adenocarcinoma cells which were transfected with a beta-galactosidase gene as marker to facilitate their detection. Intraportal injection of CC531-lac-Z cells resulted in a rapid and locally aggressive growth within the liver and was characterised by a tumour volume doubling time of 20 h and abundant angiogenesis. A commercially available chemi-luminescence assay allowed rapid, quantitative and sensitive detection of the diffusely growing tumour cells. Immunogenicity of CC531-lac-Z cells induced by the marker gene was significantly reduced by co-administering the tumour cells with matrigel. Within an observation period of three weeks following tumour cell injection only 6% of the animals showed lung involvement, thus indicating a specific homing of CC531-lac-Z cells to the liver. This period appears long enough to allow therapeutic manipulations at various stages of tumour growth in the liver. It is envisaged that the model will have applications for various therapeutic strategies.