Increased expression of IL17A in human gastric cancer and its potential roles in gastric carcinogenesis

Tumour Biol. 2014 Jun;35(6):5347-56. doi: 10.1007/s13277-014-1697-3. Epub 2014 Feb 26.

Abstract

Inflammatory cytokines modulate immune responses in the tumor microenvironment during progression. The role of interleukin (IL) 17A in cancer is currently under debate. We aim to investigate the expression of IL17A in situ tumors as well as in nontumor gastric mucosa tissues and further explore the functional significance of IL17A on gastric cancer cells in vitro. We found that compared with nontumor regions, the expression of IL17A were increased significantly in tumors of gastric cancer patients (P=0.007). The immunoreactivity for IL17A was found only in cytoplasm of inflammatory cells as well as vascular endothelial cells but not in tumor cells. Consistently, IL17A transcription was silenced in a variety of gastric cancer cell lines. In vitro, recombinant human IL17A protein promotes cell proliferation and monolayer wound healing of both AGS and SGC7901cells, in a dose-dependent manner. Besides, IL17A inhibits H2O2-induced cell apoptosis. Expression of IL6 and MMP13 mRNA was increased significantly after IL17A stimulation. These data suggest that accumulation of intratumoral IL17A-producing cells may promote gastric cancer progression directly or by inducing key signal transduction pathways implicated in gastric carcinogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Transformation, Neoplastic
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Interleukin-17 / genetics
  • Interleukin-17 / physiology*
  • Matrix Metalloproteinase 13 / physiology
  • Mice
  • Neoplasm Invasiveness
  • Stomach Neoplasms / etiology*
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / pathology

Substances

  • IL17A protein, human
  • Interleukin-17
  • Matrix Metalloproteinase 13