Analysis of the vitamin D system in cutaneous squamous cell carcinomas

Background: Increasing evidence points at an important function of vitamin D metabolites for growth regulation in various tissues, and new vitamin D analogs are interesting candidates for the treatment of malignancies, including squamous cell carcinomas (SCC). Methods: We have analyzed expression of vitamin D receptor (VDR), vitamin D-25-hydroxylase (25-OHase), 25-hydroxyvitamin D-1alpha-hydroxylase (1alpha-OHase), and 1,25-dihydroxyvitamin D-24-hydroxylase (24-OHase) in SCC. Results: Intensity of VDR immunoreactivity was increased in SCCs as compared to normal human skin. VDR staining did not correlate with histological type or grading, nor with markers for proliferation, differentiation, or apoptotic cells. Incubation of SCC cell lines (SCL-1, SCL-2) with calcitriol resulted in a dose-dependent suppression of cell proliferation (approximately up to 30%) in vitro, as measured by a tetrazolium salt (WST-1)-based colorimetric assay. RNA levels for VDR, 25-OHase, 1alpha-OHase, and 24-OHase were significantly elevated in SCCs as compared to HS, as measured by real-time polymerase chain reaction. Conclusions: Our findings demonstrate that modulation of VDR expression and local synthesis or metabolism of vitamin D metabolites may be of importance for growth regulation of SCCs. Additionally, SCCs represent potential targets for therapy with new vitamin D analogs that exert little calcemic side effects or for pharmacological modulation of calcitriol synthesis/metabolism in these tumors.