1. ¹Department of Dermatology and Interdisciplinary Center for Clinical Research (IZKF) Münster, University of Münster, Münster, Germany
2. ²Department of Pediatrics, University of Münster, Münster, Germany
3. ³Rudolf Virchow Center, DFG Research Center for Experimental Biomedicine
4. ⁴Deparment of Dermatology, University of Würzburg, Würzburg, Germany
5. ⁵Deparment of Pharmacology and Therapeutics, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada

Correspondence: Dr. M Steinhoff, Department of Dermatology, University of Münster, Von-Esmarch-Str. 58, 48149 Münster, Germany. E-Mail: msteinho@uni-muenster.de

Received 16 May 2006; Revised 6 February 2007; Accepted 20 February 2007; Published online 3 May 2007.

Abstract

The proteinase-activated receptor PAR₂ has been demonstrated to modulate tumor growth, invasion and metastasis in various tissues. However, the role of PAR₂ in cutaneous cancerogenesis is still unknown. Here we could show a protective role of PAR₂ in the development of epidermal skin tumors: we established a mouse skin tumor model using chemically induced carcinogenesis. Tumors started to appear after eight weeks. After 13 weeks, PAR₂-deficient mice showed a significantly increased number of skin tumors (14 per animal on the average) in contrast to the wild type (eight tumors per mouse). Analysis of possible signal transduction pathways activated upon PAR₂ stimulation in HaCaT keratinocytes showed an involvement of extracellular signal-regulated kinase 1/2 and profound epidermal growth factor receptor transactivation, leading to secretion of the tumor-suppressing factor transforming growth factor-1. Thus, our results provide early experimental evidence for a tumor-protective role of PAR₂.