[Cyclooxygenases in the skin].
Cyclooxygenases (COX)-1 and COX-2 catalyse the key steps of prostaglandin biosynthesis and are the major target for non-steroidal anti-inflammatory drugs. In general, COX-1 but not COX-2 is expressed in healthy tissues of adults. After incision or acute irritant dermatitis, COX-2 is induced transiently. The development of UV-induced erythema and edema as well as of skin tumours is significantly governed by COX-2 activity. Squamous cell carcinomas and actinic keratoses are prominent examples of epithelial tumours with COX-2 overexpression in the tumour parenchyma, inflammatory infiltrate and associated vessels. According to multi-stage carcinogenesis studies in mouse skin and experiments with transgenic mice, there is a causal relationship between aberrant COX-2 expression and activity in the epithelium and tumour promotion and tumour progression. The transgenic overexpression of COX-2 causes an "autopromoted" skin phenotype, i.e. it dramatically sensitizes the tissue for the development of squamous cell carcinomas. Vice versa, the genetic ablation of COX-2, as well as of COX-1, results in a reduced tumour burden in murine skin. A major mechanism by which COX-2 contributes to epidermal tumour formation seems to be the disturbance of terminal keratinocyte differentiation. Because of these data, selective COX-2 inhibitors are ranked among the most promising agents for skin cancer prevention and therapy.
Müller-Decker
Karin
K
Deutsches Krebsforschungszentrum Heidelberg, Arbeitsgruppe Eicosanoide und Tumorentwicklung. K.Mueller-Decker@DKFZ.de
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use*; D006801:Humans; D051379:Mice; D008954:Models, Biological; D017410:Practice Guidelines as Topic; D010818:Practice Patterns, Physicians'; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000378:metabolism*
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D016861:Cyclooxygenase Inhibitors; D011451:Prostaglandin-Endoperoxide Synthases