Interleukin 17A promotes hepatocellular carcinoma metastasis via NF-kB induced matrix metalloproteinases 2 and 9 expression

PLoS One. 2011;6(7):e21816. doi: 10.1371/journal.pone.0021816. Epub 2011 Jul 7.


Background: IL-17A is a pro-inflammatory cytokine that plays important role in inflammatory disease pathology and tumor microenvironment. The aim of this study is to investigate the effect of IL-17A on the progression of hepatocellular carcinoma (HCC).

Methodology and principal finding: Expression pattern of IL-17A in clinical HCC samples (n = 43) was determined by immunohistochemistry staining. Transcript levels of MMP2, MMP9 and IL-17A were measured in another 50 pairs (including tumor and related non-tumor tissues) HCC samples. Cell growth, focus formation, cell migration, invasion and western blot assays were used to characterize the functional and signaling mechanisms in IL-17A-treated HCC. Association study was used to identify clinical significance of IL-17A in HCC. Compared with paired non-tumor tissue, higher frequency of IL-17A-positive cells was detected in tumor tissues in HCCs with metastasis, and the frequency of IL-17A-positive cells was also significantly associated with poor prognosis of HCC (P = 0.01). Functional study found that IL-17A could promote HCC cell migration and invasion. Further molecular analysis also showed that IL-17A could upregulate MMP2 and MMP9 expression via NF-κB signaling activation.

Conclusions: IL-17A could promote HCC metastasis by the upregulation of MMP2 and MMP9 expression via activating NF-κB signaling pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Carcinoma, Hepatocellular / enzymology*
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / pathology*
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Enzyme Induction / drug effects
  • Epithelial-Mesenchymal Transition / drug effects
  • Female
  • Gene Expression Regulation, Enzymologic / drug effects
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Interleukin-17 / pharmacology*
  • Liver Neoplasms / enzymology
  • Liver Neoplasms / genetics
  • Liver Neoplasms / pathology*
  • Male
  • Matrix Metalloproteinase 2 / biosynthesis*
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 9 / biosynthesis*
  • Matrix Metalloproteinase 9 / genetics
  • Middle Aged
  • Multivariate Analysis
  • NF-kappa B / metabolism*
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Prognosis
  • Recombinant Proteins / pharmacology
  • Survival Analysis
  • Up-Regulation / drug effects


  • Interleukin-17
  • NF-kappa B
  • Recombinant Proteins
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9