A human carcinoma model in athymic rats reflecting solid and disseminated colorectal metastases

We studied the metastatic properties of human tumor cells and tumor cell di ssemination in a xenograft tumor model for human colorectal carcinoma in at hymic rats which shows a reproducible pattern of metastases similar to the clinical situation. Such a model is also attractive for evaluating several therapeutic approaches. The tumor cell lines HT-29 and WiDr which are deriv ed from the same colorectal tumor and exhibit a similar tumorigenic potenti al after subcutaneous injection were injected into the portal venous system of 4-week-old male nude rats. After injection of WiDr cells no liver metas tases were observed; however, 50% of the rats developed liver metastases 4- 12 weeks after injection of HT-29. Immunostaining of the liver cryosections at different times after injection revealed a total disappearance of WiDr cells within the first 12 h. A subpopulation of HT-29 (HT29-b) with increas ed metastatic activity was isolated by double selection and recultivation o f cells from induced liver metastases. After a 6- to 12-week period rats in jected with HT-29b showed a pattern of metastases with additional lung meta stases and in some cases peritoneal carcinosis. In addition to immunohistoc hemistry cytokeratin 20 reverse transcriptase-polymerase chain reaction was confirmed to be a sensitive and specific tool for the detection of dissemi nated tumor cells in different compartments.