Interleukin 17A promotes gastric cancer invasiveness via NF-κB mediated matrix metalloproteinases 2 and 9 expression

PLoS One. 2014 Jun 6;9(6):e96678. doi: 10.1371/journal.pone.0096678. eCollection 2014.

Abstract

Interleukin 17A (IL-17A), as a pro-inflammatory cytokine, is involved in pathology of inflammatory diseases and tumor microenvironment. The aim of this study is to investigate the effect of IL-17A on the invasiveness of gastric cancer (GC). In the study, we found that IL-17A could promote the migration and invasion of GC cells. Furthermore, after treated with IL-17A, the expressions and activities of matrix metalloproteinase 2 (MMP-2) and MMP-9 were upregulated, while the expressions of TIMP-1 and TIMP-2 were downregulated. Moreover, the nuclear/overall fractions of p65 and p50 were dramatically elevated by IL-17A. Pretreatment with helenalin, a nuclear factor-κB (NF-κB) inhibitor, was proved to abolish the promoting effect of IL-17A on the invasion ability of GC cells and upregulation of MMP-2 and MMP-9. In conclusion, our findings illustrated that IL-17A could promote the invasion of GC cells by activating NF-κB pathway, and subsequently upregulating the expression of MMP-2 and MMP-9. These results may lead to the identification of new diagnostic markers and therapeutic targets of GC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Interleukin-17 / pharmacology*
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / metabolism*
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • Neoplasm Invasiveness
  • Stomach Neoplasms / metabolism*
  • Tissue Inhibitor of Metalloproteinase-1 / genetics
  • Tissue Inhibitor of Metalloproteinase-1 / metabolism
  • Tissue Inhibitor of Metalloproteinase-2 / genetics
  • Tissue Inhibitor of Metalloproteinase-2 / metabolism

Substances

  • Interleukin-17
  • NF-kappa B
  • Tissue Inhibitor of Metalloproteinase-1
  • Tissue Inhibitor of Metalloproteinase-2
  • MMP2 protein, human
  • Matrix Metalloproteinase 2
  • MMP9 protein, human
  • Matrix Metalloproteinase 9