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 in vivo human studies have suggested a possible activating role of SCF on adult human melanocytes. In order to study the impact of this pathway on normal melanocyte homeostasis, human skin xenografts were treated with serial injections of recombinant human SCF or a KIT-inhibitory antibody (K44.2). On histologic evaluation, SCF injection increased, whereas KIT inhibition decreased the number, size, and dendricity of melanocytes. Immunohistochemical expression of melanocyte differentiation antigens, including tyrosinase-related-protein-1 and gp100/pmel17, was markedly increased by treatment with SCF, and decreased by K44.2 treatment. The number of Ki67-positive melanocytes was increased in the SCF-treated tissue, suggesting a direct proliferative effect of SCF; conversely, treatment with K44.2 resulted in melanocyte loss, which did not appear reversible with prolonged treatment. These findings demonstrate that the SCF/KIT pathway remains critical in adult human skin, and that pharmacologic modulation of this single pathway can control cutaneous melanocyte homeostasis.
Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA.
J M
JM
Grichnik
J A
JA
Burch
J
J
Burchette
C R
CR
Shea
D000818:Animals; D002452:Cell Count; D006706:Homeostasis; D006801:Humans; D007370:Interferon Type I / Q000032:analysis; D019394:Ki-67 Antigen / Q000032:analysis; D008544:Melanocytes / Q000187:drug effects* / Q000502:physiology; D008562:Membrane Glycoproteins; D051379:Mice; D010088:Oxidoreductases; D011506:Proteins / Q000032:analysis; D019009:Proto-Oncogene Proteins c-kit / Q000502:physiology*; D016038:Skin Transplantation; D019089:Stem Cell Factor / Q000494:pharmacology*; D014183:Transplantation, Heterologous
D007370:Interferon Type I; D019394:Ki-67 Antigen; D008562:Membrane Glycoproteins; D011506:Proteins; D019089:Stem Cell Factor; D010088:Oxidoreductases; C489799:TYRP1 protein, human; C079621:Tyrp1 protein, mouse; C064056:tyrosinase-related protein-1; D019009:Proto-Oncogene Proteins c-kit