TY - JOUR
T1 - The role of transforming growth factor-β in suppression of hepatic metastasis from colon cancer
AU - Are, Chandrakanth
AU - Simms, Neka
AU - Rajupt, Ashwani
AU - Brattain, Michael
PY - 2010/9
Y1 - 2010/9
N2 - 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.
AB - 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.
KW - Basic science < liver
KW - Colorectal metastases < liver
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U2 - 10.1111/j.1477-2574.2010.00219.x
DO - 10.1111/j.1477-2574.2010.00219.x
M3 - Article
C2 - 20815859
AN - SCOPUS:77956893381
VL - 12
SP - 498
EP - 506
JO - HPB
JF - HPB
SN - 1365-182X
IS - 7
ER -