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), 3 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 GEM. Moreover, GEM 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 delectable 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 GEM cells bearing c-Met receptor. It is also a significant angiogenesis factor in GEM, and may serve as a cellular growth factor for certain GEM cells. These lines of evidence suggest that HGF/SF signaling pathway may serve as a promising new target of therapeutic intervention of GEM.