Inflammation in epithelial skin tumours: old stories and new ideas

The essential contribution of inflammation to tumour development and progression has gained increasing acceptance. For epithelial skin cancer, the observation that tumours arise in sites of chronic irritation and inflammation dates back to 1828 and has stimulated a whole field of research. Chemically-induced mouse skin tumours requiring inflammatory agents such as 12-O-tetradecanoylphorbol 13-acetate (TPA) for tumour-promotion have greatly contributed to our understanding of multi-stage carcinogenesis and have given important insights into the functional interaction between inflammatory micro-environment and epithelial tumour, especially when used in combination with transgenic animals. Data from these and additional new model systems clearly emphasise that the tumour-promoting micro-environment is indispensable for tumour formation and progression. It strongly resembles the wound and is largely orchestrated by inflammatory cells allowing tumour cells to co-opt signalling molecules of the innate immune system to promote their growth, invasion and metastasis. Consequently, anti-inflammatory drugs are of great clinical interest in prevention and treatment of epithelial skin cancers.