The role of transforming growth factor-beta in suppression of hepatic metastasis from colon cancer.
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.
Are
Chandrakanth
C
Division of Surgical Oncology, Department of Surgery, University of Nebraska Medical Center, Omaha, NE 68198, USA. care@unmc.edu
Simms
Neka
N
Rajput
Ashwani
A
Rajupt
Ashwani
A
Brattain
Michael
M
D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control* / Q000556:secondary; D008175:Lung Neoplasms / Q000378:metabolism / Q000556:secondary; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D047368:Tumor Burden
D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D000077294:Receptor, Transforming Growth Factor-beta Type II
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