Effect of hepatocyte growth factor on invasion of prostate cancer cell lines

Oncol Rep. Jul-Aug 2003;10(4):1001-6.

Abstract

Hepatocyte growth factor (HGF) was suggested to play an important role in the regulation of mitogenesis, motogenesis, angiogenesis, migration and invasion for various types of cells, and acts through a specific membrane receptor encoded by c-met proto-oncogene. However, the mechanism of the effect of HGF on tumor invasion of prostate cancer cells remains unclear. We investigated the effect of HGF on the invasion of PC-3 and DU-145 prostate cancer cells through a reconstituted basement membrane (Matrigel), the haptotactic migration to fibronectin substrate, the expression of protein and mRNA for matrix metalloproteinases (MMP)-1 and -9, membrane-type 1-MMP (MT1-MMP), urokinase-type plasminogen activator (u-PA) and its receptor (uPAR). HGF increased both Matrigel invasion and haptotactic migration of prostate cancer cells. Furthermore, HGF also increased the production of MMP-1 and -9, MT1-MMP, u-PA and uPAR of these cells. These results suggested that HGF increased the invasive potential of prostate cancer cells probably through enhancement of cell motility and the production of MMPs and u-PA.

MeSH terms

  • Antineoplastic Agents / metabolism
  • Cell Adhesion / drug effects
  • Cell Movement / drug effects
  • Collagen
  • Drug Combinations
  • Fibrin / metabolism
  • Hepatocyte Growth Factor / pharmacology*
  • Humans
  • Laminin
  • Male
  • Matrix Metalloproteinase 1 / genetics
  • Matrix Metalloproteinase 1 / metabolism
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / metabolism
  • Neoplasm Invasiveness
  • Prostatic Neoplasms / enzymology
  • Prostatic Neoplasms / pathology*
  • Proteoglycans
  • RNA, Messenger / metabolism
  • RNA, Neoplasm / genetics
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism
  • Receptors, Urokinase Plasminogen Activator
  • Recombinant Proteins / pharmacology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tissue Inhibitor of Metalloproteinase-1 / genetics
  • Tissue Inhibitor of Metalloproteinase-1 / metabolism
  • Tumor Cells, Cultured
  • Urokinase-Type Plasminogen Activator / genetics
  • Urokinase-Type Plasminogen Activator / metabolism

Substances

  • Antineoplastic Agents
  • Drug Combinations
  • Laminin
  • PLAUR protein, human
  • Proteoglycans
  • RNA, Messenger
  • RNA, Neoplasm
  • Receptors, Cell Surface
  • Receptors, Urokinase Plasminogen Activator
  • Recombinant Proteins
  • Tissue Inhibitor of Metalloproteinase-1
  • matrigel
  • Hepatocyte Growth Factor
  • Fibrin
  • Collagen
  • Urokinase-Type Plasminogen Activator
  • Matrix Metalloproteinase 9
  • Matrix Metalloproteinase 1