Suprabasal α5β1 integrin expression stimulates formation of epidermal squamous cell carcinomas without disrupting TGFβ signaling or inducing spindle cell tumors
✍ Scribed by David M. Owens; Simon Broad; Xiaohong Yan; Salvador A. Benitah; Fiona M. Watt
- Book ID
- 102501779
- Publisher
- John Wiley and Sons
- Year
- 2005
- Tongue
- English
- Weight
- 411 KB
- Volume
- 44
- Category
- Article
- ISSN
- 0899-1987
- DOI
- 10.1002/mc.20118
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✦ Synopsis
Abstract
During epidermal chemical carcinogenesis benign papillomas convert to squamous cell carcinomas, some of which undergo epithelial‐mesenchymal conversion to highly malignant spindle cell tumors. TGFβ inhibits early stages of carcinogenesis but promotes the spindle cell phenotype in later stages. One hallmark of spindle cell tumors is upregulation of the α5β1 integrin fibronectin receptor. To examine the significance of altered α5β1 integrin expression, we induced tumors in transgenic mice expressing α5β1 in the suprabasal epidermal layers. Invα5β1 mice developed threefold more papillomas and squamous cell carcinomas than wild‐type (Wt) littermates; however, no spindle cell tumors or increased metastases were observed. Suprabasal expression of the α6β4 integrin increases squamous cell carcinoma formation and decreases TGFβ sensitivity while α3β1 may have the opposite effect. In contrast, nuclear phosphoSmad2 labeling in Invα5β1 epidermis and tumors was indistinguishable from Wt, and suprabasal α5β1 did not block TGFβ‐induced Smad2/3 translocation or growth inhibition in cultured keratinocytes. We conclude that upregulation of α5β1 does not predispose the epidermis to undergo conversion to spindle cell tumors and that the mechanism by which α5β1 influences susceptibility to carcinogenesis is independent of perturbed TGFβ signaling. © 2005 Wiley‐Liss, Inc.