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Expression of stem cell factor and its receptor by human neuroblastoma
cells and tumors
D Beck, N Gross, CB Brognara and G Perruisseau
Research Laboratory, University Hospital, Lausanne, Switzerland.
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.
Volume 86,
Issue 8,
pp. 3132-3138,
10/15/1995
Copyright © 1995 by The American Society of Hematology

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