title: 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).
  
  
  RESULTS
  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.affiliation: Department of Clinical Oncology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.forename: George Ka-Kit
authors.initials: GK
authors.lastname: Lau
authors.forename: Leilei
authors.initials: L
authors.lastname: Chen
authors.forename: Sui-sui
authors.initials: SS
authors.lastname: Dong
authors.forename: Hui-Yao
authors.initials: HY
authors.lastname: Lan
authors.forename: Xiao-Ru
authors.initials: XR
authors.lastname: Huang
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: John M
authors.initials: JM
authors.lastname: Luk
authors.forename: Yun-Fei
authors.initials: YF
authors.lastname: Yuan
authors.forename: Xin-yuan
authors.initials: XY
authors.lastname: Guan
mesh_terms: D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004790:Enzyme Induction / Q000187:drug effects; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D020381:Interleukin-17 / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis* / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis* / Q000235:genetics; D008875:Middle Aged; D015999:Multivariate Analysis; D016328:NF-kappa B / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D011379:Prognosis; D011994:Recombinant Proteins / Q000494:pharmacology; D016019:Survival Analysis; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D020381:Interleukin-17; D016328:NF-kappa B; D011994:Recombinant Proteins; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9