Simultaneous up-regulation of urokinase-type plasminogen activator (uPA) and uPA receptor by hepatocyte growth factor/scatter factor in human glioma cells.
Several lines of evidence indicate that hepatocyte growth factor/scatter factor (HGF/SF) and its receptor, c-Met, may play an important role in progression of human glioma. In this study, effects of HGF/SF on urokinase- type plasminogen activator (uPA)-mediated proteolysis network were examined in c-Met-positive human glioma cell lines. Treatment of the glioma cells with various concentrations of HGF/SF resulted in an enhanced secretion of uPA proteins accompanying increased transcription of uPA mRNA in a dose dependent fashion. The levels of uPA receptor (uPAR) mRNAs were also elevated simultaneously upon HGF/SF stimulation, and the cell-surface associated uPA activity was also elevated by the treatment. Since concomitant expression of HGF and its receptor c-Met are frequently observed in malignant gliomas, these results suggest that HGF/SF participates in invasive process of malignant glioma cells not only by its motility-stimulating activity but also through enhanced degradation of the extracellular matrix induced by autocrine activation of uPA proteolysis network.
Moriyama
T
T
Department of Neurosurgery, Miyazaki Medical College, Kiyotake, Japan.
Kataoka
H
H
Hamasuna
R
R
Yoshida
E
E
Sameshima
T
T
Iseda
T
T
Yokogami
K
K
Nakano
S
S
Koono
M
M
Wakisaka
S
S
D016543:Central Nervous System Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D005910:Glioma / Q000188:drug therapy / Q000378:metabolism*; D017228:Hepatocyte Growth Factor / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D009842:Oligopeptides / Q000378:metabolism; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D055293:Receptors, Urokinase Plasminogen Activator; D014407:Tumor Cells, Cultured; D015854:Up-Regulation; D014568:Urokinase-Type Plasminogen Activator / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*
D009842:Oligopeptides; C524898:PLAUR protein, human; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D017228:Hepatocyte Growth Factor; C028190:5-oxo-prolyl-glycyl-arginine-4-nitroanilide; D019859:Proto-Oncogene Proteins c-met; D014568:Urokinase-Type Plasminogen Activator