In vitro models of human skin and oral cancer and tissue repair

The human skin is a versatile organ composed of tissue in a constant state of self-renewal and differentiation. Tumours of the skin are often sub divided into non melanoma skin cancer (NMSC) and malignant melanoma. NMSC are the most common of all human epithelial cancers and the two most common types of NMSC are basal cells (BCC) and squamous cell carcinoma (SCC). In contrast malignant melanoma as its name implies arises from the melanocytes responsible for skin colour. Toa considerable extent skin has been a pioneer of in vitro modelling and tissue engineering and it is possible to generate excellent in vitro three-dimensional skin models. However, in spite of the availability of these in vitro skin models most cancer research is carried out on mice genetically modified to develop skin cancer. In the Blizard Institute a major focus of our research has been to usehuman skin keratinocytes genetically modified to either knock down or express proteins associated with NMSC. By using these genetically altered cells we are developing three dimensional laboratory models of human skin cancer. We aim to show that these models can be used to understand how specific pathways are involved in skin tumorigenesis and to demonstrate that such models are a viable alternative to animals. Complimentary to our work on skin cancer we also focus on oral squamous cell carcinoma, a tumour type that has an annual worldwide incidence of over 300000 cases and a mortality rate of 48%. A major aim of this research being to investigate whether diverse cancer stem cell phenotypes best be modeled in vitro, in order to accurately predict cellular behavior and response to therapy? The pioneering use of human skin as a model of tissue engineering keratinocytes has continued with work aimed at understanding how skin cells sense and respond to changes in their physical microenvironment using engineered materials and model systems to precisely control the signals presented to cells.  The ultimate goal being to translate our findings into effective strategies for skin repair.