title: Hepatocyte growth factor/c-met signaling in regulating urokinase plasminogen activator in human stomach cancer: A potential therapeutic target for human stomach cancer.
abstract: BACKGROUND
  Up-regulation of the hepatocyte growth factor (HGF), its transmembrane tyrosine kinase receptor (c-Met), and urokinase type plasminogen activator (uPA), is associated with the development and metastasis of various types of cancers. However, the mechanisms by which HGF/c-Met signaling mediates cancer progression and metastasis are unclear.
  
  
  METHODS
  We investigated the roles of HGF/c-Met in tumor progression and metastasis in NUGC-3 and MKN-28 stomach cancer cell lines.
  
  
  RESULTS
  Treatment with HGF increased c-Met phosphorylation in a dose-dependent manner, as well as increasing cell proliferation. HGF treatment also increased the protein level and the activity of uPA in NUGC-3 and MKN-28 cells. A monoclonal antibody against human uPA receptor (uPAR), mAb 3936, inhibited HGF-mediated tumor cell invasion in a dose-dependent manner. Down-regulation of uPA using uPA-shRNA induced a decrease in in vitro cell invasion in NUGC-3 cells.
  
  
  CONCLUSIONS
  These results suggest that NUGC-3 and MKN-28 cells express functional c-Met, which may provide a therapeutic target for interfering with metastases of cancer cells by inhibiting uPA and uPAR-mediated proteolysis.
authors.affiliation: Department of Hemato-oncology, Yeungnam University College of Medicine, Daegu, Korea.
authors.forename: Kyung Hee
authors.initials: KH
authors.lastname: Lee
authors.forename: Eun Young
authors.initials: EY
authors.lastname: Choi
authors.forename: Myung Soo
authors.initials: MS
authors.lastname: Hyun
authors.forename: Byung Ik
authors.initials: BI
authors.lastname: Jang
authors.forename: Tae Nyeun
authors.initials: TN
authors.lastname: Kim
authors.forename: Sang Woon
authors.initials: SW
authors.lastname: Kim
authors.forename: Sun Kyo
authors.initials: SK
authors.lastname: Song
authors.forename: Jung Hye
authors.initials: JH
authors.lastname: Kim
authors.forename: Jae-Ryong
authors.initials: JR
authors.lastname: Kim
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000201:enzymology; D018450:Disease Progression; D017228:Hepatocyte Growth Factor / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D009362:Neoplasm Metastasis; D019859:Proto-Oncogene Proteins c-met / Q000187:drug effects*; D020794:Receptor Protein-Tyrosine Kinases / Q000187:drug effects*; D017978:Receptors, Growth Factor / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects*; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000201:enzymology*; D014568:Urokinase-Type Plasminogen Activator / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D017978:Receptors, Growth Factor; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met; D020794:Receptor Protein-Tyrosine Kinases; D014568:Urokinase-Type Plasminogen Activator