Recombinant human stem cell factor (kit ligand) promotes human mast cell and melanocyte hyperplasia and functional activation in vivo.
Stem cell factor (SCF), also known as mast cell growth factor, kit ligand, and steel factor, is the ligand for the tyrosine kinase receptor (SCFR) that is encoded by the c-kit proto-oncogene. We analyzed the effects of recombinant human SCF (r-hSCF, 5-50 micrograms/kg/day, injected subcutaneously) on mast cells and melanocytes in a phase I study of 10 patients with advanced breast carcinoma. A wheal and flare reaction developed at each r-hSCF injection site; by electron microscopy, most dermal mast cells at these sites exhibited extensive, anaphylactic-type degranulation. A 14-d course of r-hSCF significantly increased dermal mast cell density at sites distant to those injected with the cytokine and also increased both urinary levels of the major histamine metabolite, methyl-histamine, and serum levels of mast cell alpha-tryptase. Five subjects developed areas of persistent hyperpigmentation at r-hSCF injection sites; by light microscopy, these sites exhibited markedly increased epidermal melanization and increased numbers of melanocytes. The demonstration that r-hSCF can promote both the hyperplasia and the functional activation of human mast cells and melanocytes in vivo has implications for our understanding of the role of endogenous SCF in health and disease. These findings also indicate that the interaction between SCF and its receptor represents a potential therapeutic target for regulating the numbers and functional activity of both mast cells and cutaneous melanocytes.
Costa
J J
JJ
Department of Pathology, Beth Israel Hospital, Harvard Medical School, Boston, Massachusetts 02215, USA.
Demetri
G D
GD
Harrist
T J
TJ
Dvorak
A M
AM
Hayes
D F
DF
Merica
E A
EA
Menchaca
D M
DM
Gringeri
A J
AJ
Schwartz
L B
LB
Galli
S J
SJ
D000707:Anaphylaxis; D001706:Biopsy; D001943:Breast Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D006965:Hyperplasia; D008407:Mast Cells / Q000187:drug effects / Q000473:pathology*; D008544:Melanocytes / Q000187:drug effects / Q000473:pathology*; D009367:Neoplasm Staging; D000090063:Proto-Oncogene Mas; D011994:Recombinant Proteins / Q000009:adverse effects; D012867:Skin / Q000473:pathology; D019089:Stem Cell Factor / Q000009:adverse effects*
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011994:Recombinant Proteins; D019089:Stem Cell Factor