Development of an HT29 liver metastases model in nude rats

The liver is the most frequent and fatal site of distant spreading of colorectal cancer. Most liver metastases animal models involve nude mice and an injection of tumour cells through the spleen or portal vein, or orthotopic implantation of tumour cells in the colon wall. The aim of this study was to develop a reliable rat model of liver metastases with human colorectal HT29 cells. Seventy male athymic Rowett nude rats weighing 300+/-30 g were separated into three groups. The first group (n=20) consisted of untreated rats, rats in the second group (n=20) were immunosuppressed by cyclosporin A, and those in the third group (n=30) were irradiated the day before cell grafting. Tumour cells (2 x 10(7)) were subcapsulary injected into the liver, and rats were sacrificed after 60 days. The livers were excised, and tumours were serially sectioned to determine size and volume, then fixed for histological studies. The take-rate was 55% in the first group, 35% in the second and 74% in the third group. The mean volume of tumours in the first group was 537+/-162 mm(3), 613+/-232 mm(3) in the second group and 2949+/-629 mm(3) in the third group. In conclusion, subcapsular injection of the human colonic HT29 cancer cells into the liver of preoperatively irradiated nude rats is a reliable, reproducible and easily obtained model, which should be useful for preclinical studies.