The role of transforming growth factor-β in suppression of hepatic metastasis from colon cancer

Background: The role of transforming growth factor-b (TGF-β) in the development of hepatic metastasis from colon cancer is not clearly elucidated. The aim of this study was to determine the role of TGF-β in the development of such metastasis. Methods: Two human colon cancer cell lines were utilized: FET-a cells (intact TGF-β inhibitory response), and CBS cells (defects in TGF-β inhibitory response caused by a deficiency in type II receptor activity). The ability of these cell lines to metastasize was analysed in an orthotopic colon cancer mouse model. Results: FET-a cells did not metastasize to the liver, but showed lung metastasis in 10% of the animals, whereas CBS cells gave rise to metastasis in 65%. Following the elimination of TGF-β activity by transfection and overexpression of dominant negative type II receptor, FET-a cells demonstrated liver and lung metastasis in 70% of the animals. Similarly, after the restoration of type II receptor activity by ectopic expression, CBS cells formed metastasis in fewer (10%) animals. Conclusions: The results of our study demonstrate for the first time that TGF-β displays selective metastasis suppressor activity. These abnormal pathways can serve as selective targets for future development of targeted therapies.