The emerging role of mast cells in skin cancers: involved cellular and molecular mechanisms

Skin cancers are the most common cancers worldwide. They can be divided into nonmelanoma skin cancers (NMSC) including basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and less common lymphomas and merkel cell carcinoma, and melanomas. Melanomas comprise less than 5% of skin cancer rate but are responsible for more than 90% of skin cancer death. Mast cells (MCs) are multifunctional cells that play an important role in inflammatory and allergic reactions. They attract other key players of the immune system by releasing cytokines. Healthy human skin comprises MCs under physiological status, and the number can increase under certain conditions including skin malignancies postulating their possible role in pathogenesis of and immunity against skin cancers. MCs respond to cytokines released by tumor stromal cells, release mediators (including histamine and tryptase), and induce the neovascularization, degradation of extracellular matrix (ECM), and induce mitogenesis. However, MCs may use molecular mechanisms to exert immunosuppressive activity including releasing complement C3, lower expression of CD40L, and overexpression of enzymes with vitamin D3 metabolizing activity including CYP27A1 and CYP27B1. This review summarizes the current knowledge on the role of MCs in pathogenesis and immunity against skin cancers.