Davies, M. and Prime, S.S. and Eveson, J.W. and Price, N. and Ganapathy, A. and D'Mello, A. and Paterson, I.C. (2012) Transforming growth factor-beta enhances invasion and metastasis in Ras-transfected human malignant epidermal keratinocytes. International Journal of Experimental Pathology, 93 (2). pp. 148-156. ISSN 0959-9673, DOI https://doi.org/10.1111/j.1365-2613.2011.00806.x.
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Abstract
Transforming growth factor- beta(TGF-beta) is known to act as a tumour suppressor early in carcinogenesis, but then switches to a pro-metastatic factor in some late stage cancers. However, the actions of TGF-beta are context dependent, and it is currently unclear how TGF-beta influences the progression of human squamous cell carcinoma (SCC). This study examined the effect of overexpression of TGF-beta 1 or TGF-beta 2 in Ras-transfected human malignant epidermal keratinocytes that represent the early stages of human SCC. In vitro, the proliferation of cells overexpressing TGF-beta 1 or TGF-beta 2 was inhibited by exogenous TGF-beta 1; cells overexpressing TGF-beta 1 also grew more slowly than controls, but the growth rate of TGF-beta 2 overexpressing cells was unaltered. However, cells that overexpressed either TGF-beta 1 or TGF-beta 2 were markedly more invasive than controls in an organotypic model of SCC. The proliferation of the invading TGF-beta 1 overexpressing cells in the organotypic assays was higher than controls. Similarly, tumours formed by the TGF-beta 1 overexpressing cells following transplantation to athymic mice were larger than tumours formed by control cells and proliferated at a higher rate. Our results demonstrate that elevated expression of either TGF-beta 1 or TGF-beta 2 in cells that represent the early stages in the development of human SCC results in a more aggressive phenotype.
| Item Type: | Article |
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| Funders: | UNSPECIFIED |
| Additional Information: | ISI Document Delivery No.: 907UK Times Cited: 2 Cited Reference Count: 28 Cited References: Adorno M, 2009, CELL, V137, P87, DOI 10.1016/j.cell.2009.01.039 Beisner J, 2006, CANCER RES, V66, P7554, DOI 10.1158/0008-5472.CAN-06-0634 Cui W, 1996, CELL, V86, P531, DOI 10.1016/S0092-8674(00)80127-0 Davies M, 2005, J CELL BIOCHEM, V95, P918, DOI 10.1002/jcb.20458 Davies M, 1997, INT J CANCER, V73, P68, DOI 10.1002/(SICI)1097-0215(19970926)73:1<68::AID-IJC12>3.0.CO;2-1 Fahey MS, 1996, BRIT J CANCER, V74, P1074, DOI 10.1038/bjc.1996.492 Fusenig NE, 1998, MOL CARCINOGEN, V23, P144, DOI 10.1002/(SICI)1098-2744(199811)23:3<144::AID-MC3>3.0.CO;2-U Ganapathy A, 2010, CANCER LETT, V298, P107, DOI 10.1016/j.canlet.2010.06.008 Gold LI, 2000, J PATHOL, V190, P579, DOI 10.1002/(SICI)1096-9896(200004)190:5<579::AID-PATH548>3.0.CO;2-I GRAYCAR JL, 1989, MOL ENDOCRINOL, V3, P1977 Han G, 2005, J CLIN INVEST, V115, P1714, DOI 10.1172/JCI24399 Hannigan A, 2010, J CLIN INVEST, V120, P2842, DOI 10.1172/JCI36125 Heldin CH, 2009, CURR OPIN CELL BIOL, V21, P166, DOI 10.1016/j.ceb.2009.01.021 Korpal M, 2010, EUR J CANCER, V46, P1232, DOI 10.1016/j.ejca.2010.02.040 Laverty HG, 2009, CYTOKINE GROWTH F R, V20, P305, DOI 10.1016/j.cytogfr.2009.07.002 Lee MK, 2007, EMBO J, V26, P3957, DOI 10.1038/sj.emboj.7601818 Letterio JJ, 1998, MINER ELECTROL METAB, V24, P161, DOI 10.1159/000057365 Massague J, 2008, CELL, V134, P220 Meulmeester E, 2011, J PATHOL, V223, P205, DOI 10.1002/path.2785 Nystrom ML, 2005, J PATHOL, V205, P468, DOI 10.1002/path.1716 PELTON RW, 1991, J CELL BIOL, V115, P1091, DOI 10.1083/jcb.115.4.1091 Portella G, 1998, CELL GROWTH DIFFER, V9, P393 Thiery J.P., 2009, CELL, V39, P871 Tobin SW, 2002, ONCOGENE, V21, P108, DOI 10.1038/sj.onc.1205026 Tsamandas AC, 2004, STRAHLENTHER ONKOL, V180, P201, DOI 10.1007/s00066-004-1149-x Vagenas K, 2007, J SURG RES, V139, P182, DOI 10.1016/j.jss.2006.10.005 Yap LF, 2009, ONCOGENE, V28, P2524, DOI 10.1038/onc.2009.105 Zhang YE, 2009, CELL RES, V19, P128, DOI 10.1038/cr.2008.328 Davies, Maria Prime, Stephen S. Eveson, John W. Price, Nicky Ganapathy, Anu D'Mello, Anita Paterson, Ian C. University of Bristol This work was supported by the University of Bristol Cancer Research Fund. Wiley-blackwell Malden |
| Uncontrolled Keywords: | invasion isoform keratinocytes SCC TGF-ss tgf-beta-3 protein expression mesenchymal transition skin carcinogenesis tumor progression patient survival transgenic mice breast-cancer in-vivo carcinomas autocrine |
| Subjects: | R Medicine > RK Dentistry |
| Divisions: | Faculty of Dentistry |
| Depositing User: | Mr Ahmad Azwan Azman |
| Date Deposited: | 08 May 2013 01:36 |
| Last Modified: | 08 May 2013 01:36 |
| URI: | http://eprints.um.edu.my/id/eprint/6035 |
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