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

Abstract

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.

• Authors: Jian Li, George Ka-Kit Lau, Leilei Chen, Sui-sui Dong, Hui-Yao Lan, Xiao-Ru Huang, Yan Li, John M Luk, Yun-Fei Yuan, Xin-yuan Guan
• Journal: PloS one (PLoS One) Vol. 6 Issue 7 Pg. e21816 ( 2011) ISSN: 1932-6203 [Electronic] United States
• PMID: 21760911 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

• Aged
• Carcinoma, Hepatocellular (enzymology, genetics, 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, genetics, pathology)
• Male
• Matrix Metalloproteinase 2 (biosynthesis, genetics)
• Matrix Metalloproteinase 9 (biosynthesis, genetics)
• Middle Aged
• Multivariate Analysis
• NF-kappa B (metabolism)
• Neoplasm Invasiveness
• Neoplasm Metastasis
• Prognosis
• Recombinant Proteins (pharmacology)
• Survival Analysis
• Up-Regulation (drug effects)