Expression of stem cell factor and its receptor by human neuroblastoma cells and tumors.
Bone marrow (BM) is a frequent site of metastasis in children with neuroblastoma (NB). Nonhematopoietic cell lines of the same neuroectodermal origin produce both stem cell factor (SCF) and its receptor, the product of the c-kit protooncogene (c-kit). Because recombinant SCF is likely to be soon clinically tested to accelerate BM recovery after high-dose chemotherapy, a treatment administered to children with disseminated NB, we addressed the question of whether SCF/c-kit complex could play a role in the proliferation and metastasis of NB cells. Northern blot analysis showed SCF mRNA transcripts in 7 of 8 (88%) NB cell lines and c-kit in 1 (13%). Neither c-kit nor SCF could be detected by Western blotting in cell extracts or by surface immunofluorescence and flow cytometry. Soluble SCF protein was detected by enzyme immunoassay at low concentrations in the cell supernatants in the same 7 NB cell lines. Treatment of 4 NB cell lines by SCF +/- cytokines relevant to BM physiology did not induce c-kit antigenic expression or modulate 3H-thymidine uptake. Likewise, the latter was not changed by incubating the cells with anti-c-kit neutralizing antibodies. Immunohistochemical analysis showed weak diffuse or focal staining for SCF and c-kit in few primary or metastatic tumor samples, only once simultaneously. We conclude that NB cell lines usually produce low levels of soluble SCF but do not express c-kit and that both proteins are rarely detected in NB tumors. The SCF/c-kit complex appears to be unlikely to stimulate NB growth or metastasis; thus, recombinant SCF could be safely administered to children with NB.
Beck
D
D
Research Laboratory, University Hospital, Lausanne, Switzerland.
Gross
N
N
Brognara
C B
CB
Perruisseau
G
G
D002455:Cell Division; D016207:Cytokines / Q000494:pharmacology; D005729:Ganglioneuroma / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D009447:Neuroblastoma / Q000378:metabolism* / Q000473:pathology; D019009:Proto-Oncogene Proteins c-kit / Q000096:biosynthesis* / Q000235:genetics; D011994:Recombinant Proteins / Q000494:pharmacology; D019089:Stem Cell Factor / Q000096:biosynthesis* / Q000235:genetics; D014407:Tumor Cells, Cultured / Q000187:drug effects
D016207:Cytokines; D009363:Neoplasm Proteins; D011994:Recombinant Proteins; D019089:Stem Cell Factor; D019009:Proto-Oncogene Proteins c-kit