THE SCF KIT PATHWAY PLAYS A CRITICAL ROLE IN THE CONTROL OF NORMAL HUMAN MELANOCYTE HOMEOSTASIS/

During development, the interaction of stem cell factor (SCF) with its receptor, KIT, is critical for the survival of melanocytes. Limited i n vivo human studies have suggested a possible activating role of SCF on adult human melanocytes. In order to study the impact of this pathw ay on normal melanocyte homeostasis, human skin xenografts were treate d with serial injections of recombinant human SCF or a KIT-inhibitory antibody (K44.2). On histologic evaluation, SCF injection increased, w hereas KIT inhibition decreased the number, size, and dendricity of me lanocytes. Immunohistochemical expression of melanocyte differentiatio n antigens, including tyrosinase-related-protein-l and gp100/pmel17, w as markedly increased by treatment with SCF, and decreased by K44.2 tr eatment. The number of Ki67-positive melanocytes was increased in the SCF-treated tissue, suggesting a direct proliferative effect of SCF; c onversely, treatment with K44.2 resulted in melanocyte loss, which did not appear reversible with prolonged treatment. These findings demons trate that the SCF/KIT pathway remains critical in adult human skin, a nd that pharmacologic modulation of this single pathway can control cu taneous melanocyte homeostasis.