Increased serum chemerin level promotes cellular invasiveness in gastric cancer: a clinical and experimental study

Peptides. 2014 Jan;51:131-8. doi: 10.1016/j.peptides.2013.10.009. Epub 2013 Nov 22.

Abstract

This study sought to determine the serum levels of chemerin in gastric cancer patients and healthy subjects and to investigate the biological effect of chemerin on gastric cancer cells. Serum chemerin level of 36 gastric cancer patients and 40 healthy subjects was measured by enzyme-linked immunosorbent assay. AGS and MKN28 cells were treated with recombinant human chemerin, MAPKs phosphorylation was then measured. Chemerin were added to culture medium of AGS and MKN28 in the absence or presence of MAPK inhibitors, VEGF, MMP-7, IL-6 and cell invasiveness assay were then performed. Serum level of chemerin was significantly higher in gastric cancer patients than healthy subjects (P<0.01). The elevation of serum chemerin level was associated with advanced clinical stages and nonintestinal type of gastric cancer. Chemerin increased invasiveness of gastric cancer cells. Chemerin induced phosphorylation of p38 and ERK1/2 MAPKs and upregulated VEGF, MMP-7 and IL-6. Inhibition of ERK1/2 phosphorylation abolished the upregulation of VEGF, MMP-7 and IL-6 and the pro-invasive effect of chemerin. This study demonstrates a novel action of chemerin in gastric carcinogenesis.

Keywords: (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; Adipokine; Chemerin; ERK1/2; Gastric cancer; IL; Invasiveness; MAPK; MMP; MTT; VEGF; extracellular signal-regulated protein kinases 1 and 2; interleukin; matrix metalloproteinase; mitogen-activated protein kinase; vascular endothelial growth factor.

MeSH terms

  • Adenocarcinoma / blood*
  • Adenocarcinoma / pathology
  • Adult
  • Aged
  • Aged, 80 and over
  • Case-Control Studies
  • Cell Line, Tumor
  • Chemokines / blood*
  • Chemokines / physiology
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Female
  • Humans
  • Imidazoles / pharmacology
  • Intercellular Signaling Peptides and Proteins
  • MAP Kinase Signaling System
  • Male
  • Middle Aged
  • Neoplasm Invasiveness
  • Phosphorylation
  • Protein Processing, Post-Translational
  • Pyridines / pharmacology
  • Receptors, Chemokine / metabolism
  • Stomach Neoplasms / blood*
  • Stomach Neoplasms / pathology
  • p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors

Substances

  • CMKLR1 protein, human
  • Chemokines
  • Imidazoles
  • Intercellular Signaling Peptides and Proteins
  • Pyridines
  • RARRES2 protein, human
  • Receptors, Chemokine
  • Extracellular Signal-Regulated MAP Kinases
  • p38 Mitogen-Activated Protein Kinases
  • SB 203580