Abstract | BACKGROUND: 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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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)
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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
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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
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