LB19
Modelling of basal cell carcinoma: investigation of senescence in basal cell carcinoma derived fibroblasts
Jane Elliott, Harshad Navsaria, Mike Philpott
Barts and the London School of Medicine and Dentistry, London, UK
Basal Cell Carcimona (BCC) is the most common form of skin cancer in the UK, occurring most commonly on sun exposed sites such as the head, neck and trunk and has been associated with mutations in genes expressed by keratinocytes. BCCs also have a complex stroma which consists of dermal fibroblasts. Dermal fibroblasts form a supportive structure through the production and release of collagens for extracellular matrices and the expression of growth factors supportive to other localised cells types. Tumour derived fibroblasts have been shown to influence the growth of other forms of epithelial cancer such as breast and prostate conferring tumourgenic properties, effecting normal growth. However, the properties of BCCs are poorly described and this is due in part to the difficulty in culturing BCCs.
The aim of this study is to develop a method for successful extraction and culture of both BCC derived keratinocytes and dermal fibroblast, characterise and study any potential stromal effects of these cells. Keratinocyte and dermal fibroblast extractions were performed on 4 mm punch biopsies. BCC derived dermal fibroblasts were grown in comparison to normal human dermal fibroblasts extracted from normal human facelift skin. Comparison of growth between normal dermal fibroblasts and BCC derived dermal fibroblasts showed BCC derived dermal fibroblasts appearing to senescence under normal culture conditions. Immunocytochemistry using Beta Galactosidase was used to confirm this indicating that once removed from the influence of BCC epithelium, BCC derived dermal fibroblasts tended towards senescence with continued passage. Quantitative Real Time-PCR showed an increase in expression levels of markers for senescence. Positive immunostaining of BCC for Gli 1 suggests that paracrine signalling may be important in the maintenance of the BCC stroma and hence BCC tumour growth.
