HEPATOCYTE GROWTH-FACTOR IS A MITOGEN FOR SCHWANN-CELLS AND IS PRESENT IN NEUROFIBROMAS

To characterize mitogens that might contribute to Schwann cell prolife ration during development or in tumors, we tested the ability of hepat ocyte 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 grow th 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 additio n of transforming growth factor beta (TGF beta) or fibroblast growth f actor (FGF). HGF is probably not a component of the axonal signal thou ght to cause Schwann cell division during development, as anti-HGF neu tralizing antibodies failed to block neuron-stimulated Schwann cell pr oliferation. In contrast, mitogenic activity present in normal human a dult nerves and in neurofibromas from patients with type 1 neurofibrom atosis 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.