Abstract 1516: Melanocyte activation by UVR-induced calprotectin.

Abstract Melanoma is the most common cause of skin cancer death, although it accounts for only 5% of all skin cancers. Epidemiologic and clinical observations have shown that the ultraviolet (UVR) component of sunlight is the most important etiologic factor in melanoma; however, the precise mechanisms by which UVR drives melanomagenesis are unknown. Mutations in oncogenes and tumor suppressor genes have been identified in melanomas, but most of these are not the UVR signature mutations found in non-melanoma skin cancers. This suggests an indirect role for UVR in melanomagenesis, likely as a tumor promoter. UVR is a potent inducer of keratinocyte-derived paracrine and melanocyte/melanoma cell-derived autocrine factors that profoundly affect melanocyte/melanoma cell gene expression and behavior. Many of these mediators are also potent proinflammatory signals that create an inflammatory environment with additional effects on untransformed and transformed melanocytes. We have identified calprotectin, a secreted heterodimer of S100A8 and A9, as one of these mediators. UVR exposure induces S100A8 and A9 transcription in and calprotectin release from human keratinocytes and melanocytes. Human melanocytes and melanoma cells constitutively express TLR4, one of the receptors for calprotectin. Treatment of human melanocytes and melanoma cells with exogenous calprotectin enhances their proliferation, migration, and invasiveness. UVR-induced calprotectin secretion by melanocytes/melanoma cells and surrounding keratinocytes activates melanocytes/melanoma cells and may thus promote melanomagenesis. Citation Format: Kristine von Maltzan, Stephanie H. Shirley, Donna F. Kusewitt. Melanocyte activation by UVR-induced calprotectin. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1516. doi:10.1158/1538-7445.AM2013-1516