Urokinase type plasminogen activator and its receptor regulate the invasive potential of gastric cancer cell lines

Int J Oncol. 2000 Nov;17(5):1001-5. doi: 10.3892/ijo.17.5.1001.

Abstract

To assess the role of urokinase-type plasminogen activator (uPA) and uPA receptor (uPAR) on the invasive potential of cancer cells, in vitro experiments were performed using two human gastric cancer cell lines, NUGC-3 and MKN-28. NUGC-3 cells secreted a higher level of uPA than MKN-28 cells, while the uPAR expression of NUGC-3 cells was lower than that of MKN-28 cells. Both cancer cell lines expressed Met protein and did not express hepatocyte growth factor (HGF). In Matrigel invasion assay, MKN-28 cells demonstrated significantly lower invasion index than NUGC-3 cells. The addition of exogenous uPA significantly increased the invasive activity of MKN-28 cells. The uPA expression in NUGC-3 cells was enhanced by adding conditioned media of fibroblast cells or HGF. These results suggest that uPA promotes the invasive capacity of the uPAR-positive cancer cells, and that stromal cells may play an important role in cancer cell invasion by supplying uPA and/or promoting uPA production.

Publication types

  • Comparative Study

MeSH terms

  • Adenocarcinoma / enzymology
  • Adenocarcinoma / pathology*
  • Cell Differentiation
  • Cell Line
  • Culture Media, Conditioned / pharmacology
  • Fibroblasts / metabolism
  • Gene Expression Regulation, Neoplastic / drug effects
  • Hepatocyte Growth Factor / metabolism
  • Hepatocyte Growth Factor / pharmacology
  • Humans
  • Neoplasm Invasiveness / physiopathology*
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / physiology*
  • RNA, Messenger / biosynthesis
  • RNA, Neoplasm / biosynthesis
  • Receptors, Cell Surface / biosynthesis
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / physiology*
  • Receptors, Urokinase Plasminogen Activator
  • Stomach Neoplasms / enzymology
  • Stomach Neoplasms / pathology*
  • Stromal Cells / metabolism
  • Tumor Cells, Cultured / drug effects
  • Tumor Cells, Cultured / enzymology
  • Urokinase-Type Plasminogen Activator / biosynthesis
  • Urokinase-Type Plasminogen Activator / genetics
  • Urokinase-Type Plasminogen Activator / pharmacology
  • Urokinase-Type Plasminogen Activator / physiology*

Substances

  • Culture Media, Conditioned
  • Neoplasm Proteins
  • PLAUR protein, human
  • RNA, Messenger
  • RNA, Neoplasm
  • Receptors, Cell Surface
  • Receptors, Urokinase Plasminogen Activator
  • Hepatocyte Growth Factor
  • Urokinase-Type Plasminogen Activator