TITLE

Interleukin 23 Promotes Hepatocellular Carcinoma Metastasis via NF-Kappa B Induced Matrix Metalloproteinase 9 Expression

AUTHOR(S)
Jian Li; Lau, George; Chen, Leilei; Yun-Fei Yuan; Huang, Jun; Luk, John M.; Xie, Dan; Xin-Yuan Guan; Coleman, William B.
PUB. DATE
September 2012
SOURCE
PLoS ONE;Sep2012, Vol. 7 Issue 9, Special section p1
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Background: Hepatocellular carcinoma (HCC) is one of the most popular cancers in the world with poor prognosis, which often develops from chronic liver inflammatory diseases. Interleukin 23 (IL-23) is an inflammatory cytokine which is reported to play an important role in tumor development in animal model. While the function of IL-23 in HCC development remains unknown, so we investigate the role of IL-23 in HCC progression in this study. Methodology and Principal Finding: Transcript level of IL-23, interleukin17A (IL-17A) and matrix metalloproteinases 9 (MMP9) in clinical HCC samples (n = 81) was determined by qPCR. Protein expression pattern of IL-23 in primary and metastatic HCC tissues pairs (n = 49 pairs) was determined by immunohistochemistry staining. Cell migration, invasion, RNA interfering and immune blotting were used to characterize the functional and signaling mechanisms in IL-23-treated HCC. Compared with paired non-tumor tissue, higher IL-23 expression was detected in HCC tumor tissues with metastasis. Immunohistochemistry staining confirmed the high expression of IL-23 in metastasis HCC. Immune blotting demonstrated that IL-23 was highly expressed in HCC cell lines with metastasis. Functional study found that IL-23 could promote HCC cell migration and invasion. Molecular analysis revealed that IL-23 could upregulate MMP9 expression via NF-κB/p65 signaling activation and IL-17A could improve IL-23 expression in tumor cells directly via activating NF-κB/p65 signaling pathway. Conclusions: IL-23 could promote HCC metastasis by the upregulation of MMP9 expression via activating NF-κB/p65 signaling pathway. At the same time, IL-17A could further promote IL-23 expression in HCC tumor cells.
ACCESSION #
82447903

 

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