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

BACKGROUND: Tissue inflammation and remodeling have been extensively studied in various tumors in relation with their invasiveness and metastasis. OBJECTIVE: The purpose of this study was to investigate the change in tissue inflammation and remodeling markers in cutaneous squamous cell carcinoma (SCC). METHODS: Expression 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. RESULTS: mRNA 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. CONCLUSION: COX-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.