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Journal of Neuroscience, Vol 14, 7284-7290, Copyright © 1994 by Society for Neuroscience
Hepatocyte growth factor is a mitogen for Schwann cells and is present in neurofibromas
A Krasnoselsky, MJ Massay, MC DeFrances, G Michalopoulos, R Zarnegar and N Ratner
Department of Anatomy and Cell Biology, University of Cincinnati School of Medicine, Ohio 45267-0521.
To characterize mitogens that might contribute to Schwann cell
proliferation during development or in tumors, we tested the ability of
hepatocyte growth factor (HGF) to stimulate Schwann cell division in vitro.
HGF is a potent mitogen for purified rat Schwann cells; DNA synthesis in
rat Schwann cells was stimulated 20-40-fold by 3-10 ng/ml HGF. Rat Schwann
cells express c-met mRNA, encoding the HGF receptor, but not HGF mRNA,
implying that HGF might act as a paracrine Schwann cell growth factor.
HGF-stimulated Schwann cell proliferation differs from that of previously
described Schwann cell mitogens in that its activity is abolished by
forskolin and is not inhibited or potentiated by addition of transforming
growth factor beta (TGF beta) or fibroblast growth factor (FGF). HGF is
probably not a component of the axonal signal thought to cause Schwann cell
division during development, as anti-HGF neutralizing antibodies failed to
block neuron-stimulated Schwann cell proliferation. In contrast, mitogenic
activity present in normal human adult nerves and in neurofibromas from
patients with type 1 neurofibromatosis analyzed in the absence of forskolin
is largely inhibitable by anti-HGF. Thus, HGF is a novel mitogen for
Schwann cells in vitro and it is present in Schwann cell tumors, suggesting
a potential role for HGF after wounding of peripheral nerves or in tumor
growth.
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