JOURNAL ARTICLE

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

Chandrakanth Are, Neka Simms, Ashwani Rajput, Ashwani Rajupt, Michael Brattain
HPB: the Official Journal of the International Hepato Pancreato Biliary Association 2010, 12 (7): 498-506
20815859

BACKGROUND: The role of transforming growth factor-beta (TGF-beta) 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-beta in the development of such metastasis.

METHODS: Two human colon cancer cell lines were utilized: FET-alpha cells (intact TGF-beta inhibitory response), and CBS cells (defects in TGF-beta 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-alpha 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-beta activity by transfection and overexpression of dominant negative type II receptor, FET-alpha 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-beta displays selective metastasis suppressor activity. These abnormal pathways can serve as selective targets for future development of targeted therapies.

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