The E7 protein of cutaneous human papillomavirus type 8 causes invasion of human keratinocytes into the dermis in organotypic cultures of skin
Article
Akgul, B., Garcia-Escudero, R., Ghali, L., Pfister, H., Fuchs, P., Navsaria, H. and Storey, A. 2005. The E7 protein of cutaneous human papillomavirus type 8 causes invasion of human keratinocytes into the dermis in organotypic cultures of skin. Cancer Research. 65 (6), pp. 2216-2223. https://doi.org/10.1158/0008-5472.CAN-04-1952
Type | Article |
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Title | The E7 protein of cutaneous human papillomavirus type 8 causes invasion of human keratinocytes into the dermis in organotypic cultures of skin |
Authors | Akgul, B., Garcia-Escudero, R., Ghali, L., Pfister, H., Fuchs, P., Navsaria, H. and Storey, A. |
Abstract | Human papillomaviruses (HPV) have been implicated in the development of nonmelanoma skin cancer (NMSC). The molecular mechanisms by which these viruses contribute towards NMSC are poorly understood. We have used an in vitro skin-equivalent model generated by transducing primary adult human epidermal keratinocytes with retroviruses expressing HPV genes to investigate the mechanisms of viral transformation. In this model, keratinocytes expressing HPV genes are seeded onto a mesenchyme composed of deepidermalized human dermis that had been repopulated with primary dermal fibroblasts. Expression of the HPV8 E7 gene caused both an enhancement of terminal differentiation and hyperproliferation, but most strikingly, the acquisition of the ability to migrate and invade through the underlying dermis. The basement membrane integrity was disrupted in a time-dependent manner in areas of invading keratinocytes, as evidenced by immunostaining of its protein components collagen types VII, IV, and laminin 5. This was accompanied by the overexpression of extracellular matrix metalloproteinases MMP-1, MMP-8, and MT-1-MMP. These results suggest that the cutaneous HPV type 8 that is frequently found in NMSC of epidermodysplasia verruciformis patients may actively promote an invasive keratinocyte phenotype. These findings also highlight the importance of epithelial-extracellular matrix-mesenchymal interactions that are required to support cell invasion. |
Research Group | Biomarkers for Cancer group |
Publisher | American Association for Cancer Research |
Journal | Cancer Research |
ISSN | 0008-5472 |
Publication dates | |
15 Mar 2005 | |
Publication process dates | |
Deposited | 19 Jun 2009 |
Output status | Published |
Additional information | PubMed PMID: 15781634. |
Digital Object Identifier (DOI) | https://doi.org/10.1158/0008-5472.CAN-04-1952 |
Language | English |
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