Epidermolysis bullosa is a group of inherited skin fragility diseases varying in severity from mild scarring to infant mortality. Great efforts are being undertaken to develop therapeutic strategies to treat the more pernicious forms of this disease, particularly those associated with recessive, loss-of-function mutations. In such cases significant effort is directed toward delivering recombinant protein at levels sufficient to demonstrate clinical benefit. Recessive dystrophic epidermolysis bullosa (RDEB) predisposes patients to a high incidence of life-threatening cutaneous squamous cell carcinoma (cSCC). Mutations in the gene encoding type VII collagen, COL7A1, are the sole cause of this disease and conflicting reports concerning type VII collagen and COL7A1 in carcinogenesis exist.Objectives
To investigate potential oncogenic effects of expressing recombinant type VII collagen in patient cells.Methods
We used retroviral transduction to introduce type VII collagen into keratinocytes derived from patients with and without RDEB.Results
Retroviral expression of type VII collagen in cSCC keratinocytes established from patients with RDEB resulted in increased cell adhesion, migration and invasion coupled with a concurrent increase in PI3K and MAPK signalling.Conclusions
Our data suggest caution when formulating strategies where delivery of type VII collagen is likely to exceed levels seen under normal physiological conditions in a patient group with a higher inherent risk of developing skin cancer.Conclusions
What's already known about this topic?Conclusions
What does this study add?