Presence of autocrine hepatocyte growth factor-Met signaling and its role in proliferation and migration of SNU-484 gastric cancer cell line

Exp Mol Med. 2005 Jun 30;37(3):213-9. doi: 10.1038/emm.2005.29.

Abstract

Autocrine stimulation via coexpression of hepatocyte growth factor (HGF) and its receptor (Met) has been reported in many human sarcomas, but few in carcinomas. In this report, we found that one gastric cancer cell line, SNU-484, among 11 gastric cell lines tested has an autocrine HGF- Met stimulation. RT-PCR, ELISA and scattering assay using MDCK cells revealed that SNU-484 cells secreted a significant amount of active HGF (about 1.25 +/- 0.41 ng/24 h/10(6) cells) into conditioned medium. Resultantly, Met in this cell line was constitutively phosphorylated. Neutralizing antibodies against HGF reduced the tyrosine phosphorylation of Met, resulting in the inhibition of cell proliferation and migration (P <0.005). To the best of our knowledge, this is the first report on autocrine HGF-Met signaling in a gastric cancer cell line. Our observations with SNU-484 cells suggest that HGF is involved in the development and/or progression of some gastric carcinoma through an autocrine mechanism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Neoplasm / immunology
  • Autocrine Communication*
  • Cell Movement*
  • Cell Proliferation
  • Culture Media, Conditioned / pharmacology
  • Dogs
  • Enzyme-Linked Immunosorbent Assay
  • Hepatocyte Growth Factor / immunology
  • Hepatocyte Growth Factor / pharmacology*
  • Neutralization Tests
  • Phosphorylation
  • Proto-Oncogene Proteins c-met / genetics
  • Proto-Oncogene Proteins c-met / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Stomach Neoplasms / immunology*
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology
  • Tumor Cells, Cultured
  • Tyrosine / metabolism

Substances

  • Antibodies, Neoplasm
  • Culture Media, Conditioned
  • Tyrosine
  • Hepatocyte Growth Factor
  • Proto-Oncogene Proteins c-met