Role for the stem cell factor/KIT complex in Schwann cell neoplasia and mast cell proliferation associated with neurofibromatosis.
Schwann cells are the primary cell type in the disfiguring lesions associated with neurofibromatosis type 1 (NF-1). These lesions also contain abnormally high numbers of mast cells, a cell type which develops in response to stem cell factor. We report here that neonatal and adult rat and human Schwann cells, as well as a transfected rat Schwann cell line and a human Schwannoma line derived from an NF-1 patient, all produced stem cell factor mRNA and protein. In coculture experiments, surface expression of stem cell factor by neonatal rat Schwann cells was profoundly downregulated by contact with dorsal root ganglion neurites. The receptor for stem cell factor, KIT, was not expressed in normal Schwann cells but was expressed in the human Schwannoma line, suggesting that aberrant KIT expression may form an autocrine loop in certain Schwann cell neoplasias.
Ryan
J J
JJ
Department of Microbiology and Immunology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298.
Klein
K A
KA
Neuberger
T J
TJ
Leftwich
J A
JA
Westin
E H
EH
Kauma
S
S
Fletcher
J A
JA
DeVries
G H
GH
Huff
T F
TF
D000818:Animals; D001483:Base Sequence; D002455:Cell Division; D002460:Cell Line; D017077:Culture Media, Conditioned; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008407:Mast Cells / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009442:Neurilemmoma / Q000378:metabolism / Q000503:physiopathology*; D009456:Neurofibromatosis 1 / Q000503:physiopathology*; D015345:Oligonucleotide Probes; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D019009:Proto-Oncogene Proteins c-kit; D051381:Rats; D017207:Rats, Sprague-Dawley; D020794:Receptor Protein-Tyrosine Kinases / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D016184:Receptors, Colony-Stimulating Factor / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D012583:Schwann Cells / Q000378:metabolism / Q000502:physiology*; D014407:Tumor Cells, Cultured
D017077:Culture Media, Conditioned; D015345:Oligonucleotide Probes; D011518:Proto-Oncogene Proteins; D016184:Receptors, Colony-Stimulating Factor; D019009:Proto-Oncogene Proteins c-kit; D020794:Receptor Protein-Tyrosine Kinases