Up-Regulation of Cyclooxygenase 2 and Matrix Metalloproteinases-2 and -9 in Cutaneous Squamous Cell Carcinoma: Active Role of Inflammation and Tissue Remodeling in Carcinogenesis

Abstract

BackgroundTissue inflammation and remodeling have been extensively studied in various tumors in relation with their invasiveness and metastasis.ObjectiveThe purpose of this study was to investigate the change in tissue inflammation and remodeling markers in cutaneous squamous cell carcinoma (SCC).MethodsExpression levels of cyclooxygenase-2 (COX-2) as an inflammatory marker and matrix metalloproteinases-2 and -9 (MMPs 2/9) as remodeling markers were studied in mouse and human SCCs. Western blot analysis and RT-PCR for COX-2 and MMPs 2/9 were performed with skin samples from SCC patients and chronic ultraviolet B (UVB)-induced SCC from hairless mice.ResultsmRNA and protein levels of COX-2 and MMPs 2/9 were up-regulated with the higher sensitivity for MMP-9 in mouse SCCs, which were induced by chronic UVB irradiation. Consistently, COX-2 and MMPs 2/9 were up-regulated with the higher sensitivity for MMP-9 in human SCCs.ConclusionCOX-2 and MMPs 2/9 are up-regulated in well-differentiated cutanous SCC. Our findings indicate that inflammatory and tissue remodeling processes are actively induced during carcinogenesis of cutaneous SCC.