Expression of hepatocyte growth factor/scatter factor and its receptor c-Met in brain tumors: evidence for a role in progression of astrocytic tumors (Review).
Hepatocyte growth factor (HGF) is a multifunctional cytokine which is believed to have important roles in tissue development and regeneration, and tumor progression. It is indistinguishable from scatter factor (SF), a motility factor. HGF/SF is believed to be a mesenchymal cell-derived cytokine acting for epithelial cells bearing its receptor tyrosine kinase, c-Met. Recently, we found that glioblastoma multiforme (GBM), a highly malignant brain tumor of astrocytic origin, concomitantly express HGF/SF and c-Met. This finding indicates a presence of autocrine loop of HGF/SF signaling pathway in GBM. Moreover, GBM cells also co-express HGF activator, a recently identified serine proteinase having efficient HGF/SF activating activity. The expression of HGF/SF and c-Met was low or hardly detectable in low-grade astrocytoma, and c-Met immunoreactivity was correlated with the histological grade of the tumor suggesting that the creation of HGF/SF autocrine loop occurs along with the progression of astrocytic brain tumors. Experimental evidence indicated that HGF/SF exhibits potent migration/invasion-inducing activity for GBM cells bearing c-Met receptor. It is also a significant angiogenesis factor in GBM, and may serve as a cellular growth factor for certain GBM cells. These lines of evidence suggest that HGF/SF signaling pathway may serve as a promising new target of therapeutic intervention of GBM.
Moriyama
T
T
Department of Neurosurgery, Miyazaki Medical College, Kiyotake, Miyazaki 889-1692, Japan.
Kataoka
H
H
Koono
M
M
Wakisaka
S
S
D001932:Brain Neoplasms / Q000209:etiology / Q000378:metabolism*; D015870:Gene Expression; D005909:Glioblastoma / Q000209:etiology / Q000378:metabolism*; D017228:Hepatocyte Growth Factor / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008959:Models, Neurological; D009361:Neoplasm Invasiveness; D009420:Nervous System / Q000378:metabolism; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met