Simultaneous up-regulation of urokinase-type plasminogen activator (uPA) and uPA receptor by hepatocyte growth factor/scatter factor in human glioma cells

Clin Exp Metastasis. 1999;17(10):873-9. doi: 10.1023/a:1006729611241.


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.

MeSH terms

  • Central Nervous System Neoplasms / drug therapy
  • Central Nervous System Neoplasms / metabolism*
  • Glioma / drug therapy
  • Glioma / metabolism*
  • Hepatocyte Growth Factor / metabolism*
  • Hepatocyte Growth Factor / pharmacology
  • Humans
  • Oligopeptides / metabolism
  • Proto-Oncogene Proteins c-met / metabolism
  • Receptors, Cell Surface / drug effects
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism*
  • Receptors, Urokinase Plasminogen Activator
  • Tumor Cells, Cultured
  • Up-Regulation
  • Urokinase-Type Plasminogen Activator / drug effects
  • Urokinase-Type Plasminogen Activator / genetics
  • Urokinase-Type Plasminogen Activator / metabolism*


  • Oligopeptides
  • PLAUR protein, human
  • Receptors, Cell Surface
  • Receptors, Urokinase Plasminogen Activator
  • Hepatocyte Growth Factor
  • 5-oxo-prolyl-glycyl-arginine-4-nitroanilide
  • Proto-Oncogene Proteins c-met
  • Urokinase-Type Plasminogen Activator