Met and hepatocyte growth factor/scatter factor expression in human gliomas.
Using double immunofluorescence staining and quantitative confocal laser scan microscopy, we show that the intensity of hepatocyte growth factor/scatter factor (HGF/SF) and Met staining in human primary brain tumors increases with the grade of malignancy and is prevalent in both the infiltrating tumor cells and endothelial hyperplastic areas. HGF/SF 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 lines 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 through Met is negatively regulated in NHA cells.
Koochekpour
S
S
ABL-Basic Research Program, National Cancer Institute, Frederick Cancer Research and Development Center, Maryland 21702, USA.
Jeffers
M
M
Rulong
S
S
Taylor
G
G
Klineberg
E
E
Hudson
E A
EA
Resau
J H
JH
Vande Woude
G F
GF
D016475:3T3 Cells; D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism*; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D005909:Glioblastoma / Q000378:metabolism / Q000473:pathology; D005910:Glioma / Q000378:metabolism* / Q000473:pathology; D017228:Hepatocyte Growth Factor / Q000096:biosynthesis* / Q000494:pharmacology; D006801:Humans; D051379:Mice; D009024:Morphogenesis; D009361:Neoplasm Invasiveness; D019859:Proto-Oncogene Proteins c-met / Q000096:biosynthesis*; D011994:Recombinant Proteins / Q000096:biosynthesis; D014162:Transfection; D014407:Tumor Cells, Cultured
D011994:Recombinant Proteins; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met