Autocrine/Paracrine Loop Between SCF/c-Kit Mast Cells Promotes Cutaneous Melanoma Progression

c-Kit, or mast/stem cell growth factor receptor Kit, is a tyrosine kinase receptor structurally analogous to the colony-stimulating factor-1 (CSF-1) and platelet-derived growth factor (PDGF) CSF-1/PDGF receptor Tyr-subfamily. It binds the cytokine KITLG/SCF to regulate cell survival and proliferation, hematopoiesis, stem cell maintenance, gametogenesis, mast cell development, migration and function, and it plays an essential role in melanogenesis. SCF and c-Kit are biologically active as membrane-bound and soluble forms. They can be expressed by tumor cells and cells of the microenvironment playing a crucial role in tumor development, progression, and relapses. To date, few investigations have concerned the role of SCF/c-Kit mast cells in normal, premalignant, and malignant skin lesions that resemble steps of malignant melanoma progression. In this study, by immunolabeling reactions, we demonstrated that in melanoma lesions, SCF and c-Kit were expressed in mast cells and released by themselves, suggesting an autocrine/paracrine loop might be implicated in regulatory mechanisms of neoangiogenesis and tumor progression in human melanoma.