MET AND HEPATOCYTE GROWTH-FACTOR SCATTER FACTOR EXPRESSION IN HUMAN GLIOMAS

Using double immunofluorescence staining and quantitative confocal las er scan microscopy, we show that the intensity of hepatocyte growth fa ctor/scatter factor (HGF/SF) and Met staining in human primary brain t umors increases with the grade of malignancy and is prevalent in both the infiltrating tumor cells and endothelial hyperplastic areas, HGF/S F and Met also are expressed in vitro in glioblastoma multiforme cell lines as well as in normal human astrocyte (NHA) cells, Moreover, HGF/ SF stimulates tyrosine phosphorylation of Met in both glioma cell line s and NHA cells, but only the glioma cell lines proliferate and become motile and invasive in response to HGF/SF, whereas the NHA cells are nonresponsive, These results implicate autocrine/paracrine Met-HGF/SF signaling in glioma tumorigenesis and suggest that HGF/SF signaling th rough Met is negatively regulated in NHA cells.