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Expression of stem cell factor and c-kit in human neuroblastoma. The
Children's Cancer Group
PS Cohen, JP Chan, M Lipkunskaya, JL Biedler and RC Seeger
Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, CA.
During development, mice with mutations of stem cell factor (SCF) or its
receptor c-kit exhibit defects in melanogenesis, as well as hematopoiesis
and gonadogenesis. Because melanocytes derive from neural crest cells, the
role of SCF and c-kit was investigated in the neural crest-derived
childhood tumor neuroblastoma. Using reverse transcription-polymerase chain
reaction analysis, simultaneous expression of steady-state mRNA for the SCF
ligand and its receptor c- kit was found in 14 of 14 (100%) human
neuroblastoma cell lines and clones and in 8 of 18 (45%) human
neuroblastoma tumor samples. Functional blockade of c-kit receptors in the
cell lines SK-N-BE(2) and SH-SY5Y using the mouse monoclonal anti-c-kit
antibody SR-1 resulted in a significant decrease in cellular growth rate
when measured by either 3H-thymidine incorporation or clonogenicity. In
addition, higher levels of c-kit mRNA expression were associated with
parental neuroblastoma cell lines and subclones with a neuronal (N)
differentiation phenotype, whereas lower levels of c-kit mRNA were
associated with neuroblastoma cell line subclones having a
schwannian/glial/melanocytic pattern of differentiation. However, the
differentiation phenotype of neuroblastoma cell lines was not directly
altered when c-kit expression was blocked using the SR-1 antibody. In
summary, these data indicate that c-kit receptor expression may play a
significant role in the growth regulation of the two neuroblastoma cell
lines examined and suggest that c-kit may also play a similar role in
neuroblastoma growth regulation in vivo. Simultaneous expression of SCF and
c-kit mRNA in both neuroblastoma cell lines and tumors implies that c-kit
may act as part of an autocrine growth loop in conjunction with endogenous
production of SCF in this disease.
Volume 84,
Issue 10,
pp. 3465-3472,
11/15/1994
Copyright © 1994 by The American Society of Hematology
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