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

Abstract

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.

• Authors: Chandrakanth Are, Neka Simms, Ashwani Rajput, Ashwani Rajupt, Michael Brattain
• Journal: HPB : the official journal of the International Hepato Pancreato Biliary Association (HPB (Oxford)) Vol. 12 Issue 7 Pg. 498-506 (Sep 2010) ISSN: 1477-2574 [Electronic] England
• PMID: 20815859 (Publication Type: Journal Article)

Chemical References

• Receptors, Transforming Growth Factor beta
• Transforming Growth Factor beta
• Protein Serine-Threonine Kinases
• Proto-Oncogene Proteins c-akt
• Receptor, Transforming Growth Factor-beta Type II

Topics

• Animals
• Cell Line, Tumor
• Cell Proliferation
• Cell Survival
• Colonic Neoplasms (genetics, metabolism, pathology)
• Humans
• Liver Neoplasms (genetics, metabolism, prevention & control, secondary)
• Lung Neoplasms (metabolism, secondary)
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Neoplasm Invasiveness
• Phosphorylation
• Protein Serine-Threonine Kinases (genetics, metabolism)
• Proto-Oncogene Proteins c-akt (metabolism)
• Receptor, Transforming Growth Factor-beta Type II
• Receptors, Transforming Growth Factor beta (genetics, metabolism)
• Signal Transduction
• Time Factors
• Transfection
• Transforming Growth Factor beta (metabolism)
• Tumor Burden