Transforming growth factor-β enhances invasion and metastasis in Ras-transfected human malignant epidermal keratinocytes

被引：17
作者：
Davies, Maria [3 ]
Prime, Stephen S. [3 ]
Eveson, John W. [3 ]
Price, Nicky [3 ]
Ganapathy, Anu [3 ]
D'Mello, Anita [3 ]
Paterson, Ian C. [1 ,2 ]
机构：
[1] Univ Malaya, Fac Dent, Dent Res & Training Unit, Kuala Lumpur 50603, Malaysia
[2] Univ Malaya, Fac Dent, Oral Canc Res Coordinating Ctr, Kuala Lumpur 50603, Malaysia
[3] Univ Bristol, Sch Oral & Dent Sci, Bristol, Avon, England
来源：
INTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY | 2012年 / 93卷 / 02期
关键词：
invasion; isoform; keratinocytes; SCC; TGF-ss; TGF-BETA-3 PROTEIN EXPRESSION; MESENCHYMAL TRANSITION; TUMOR PROGRESSION; IN-VIVO; CARCINOMAS; AUTOCRINE; ROLES; SMAD;
D O I：
10.1111/j.1365-2613.2011.00806.x
中图分类号：
R36 [病理学];
学科分类号：
100104 ;
摘要：
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.
引用
收藏
页码：148 / 156
页数：9
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