Ablation of osteopontin expression suppresses UVB-induced carcinogenesis

AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA 2237 Nonmelanoma skin cancer comprising of basal cell carcinoma and squamous cell carcinoma (SCC) is the most prevalent malignancy in Caucasian. Cutaneous SCC is a life threatening malignancy as it has the potential to metastasize and its incidence is increasing each year in the United States. It is clear that prolonged exposure to ultraviolet radiation (UVB) leads to genetic changes in skin cells producing initiated cells, but prolonged UVB exposure may also lead to changes in the microenvironment that in turn contributes to carcinogenesis. Osteopontin (OPN) is a matricellular protein that has been shown to be elevated in several cancer types. We have recently shown that OPN is highly expressed in both actinic keratoses (precursor to SCC) and human cutaneous SCC. We therefore tested whether UVB-induces increase secretion of the OPN in an animal model and whether OPN contributes to photocarcinogenesis. The dorsal skins of female OPN null and wild-type mice in 129S6/SvEv genetic background were subjected to 200 mJ/cm2 of UVB for 43 weeks. Our short term studies of UVB-treated 129/SvEv mice indicate that OPN was induced as early as 24 h after UVB exposure. Further, the percent of mice with tumors and the number of tumors per mouse were higher in 129S6/SvEv mice than OPN null mice on the same genetic background. TUNEL analyses of UVB treated dorsal skin revealed that 2.5-fold more apoptotic basal cells were present in the OPN null than wild-type mice. These data confirm and extend our findings in the two-stage skin chemical carcinogenesis model by indicating that induced expression of OPN during carcinogenesis provides an altered microenvironment for the increased transformation of initiated cells.