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

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

Jian Li  1 , 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
Affiliations

"VSports在线直播" Interleukin 17A promotes hepatocellular carcinoma metastasis via NF-kB induced matrix metalloproteinases 2 and 9 expression

Jian Li et al. PLoS One. 2011.

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). VSports手机版.

Methodology and principal finding: Expression pattern of IL-17A in clinical HCC samples (n = 43) was determined by immunohistochemistry staining V体育安卓版. 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. V体育ios版.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Expression and prognosis of IL-17A in HCC.
(A), Representatives of IL-17A expression in primary HCCs (tumor vs non-tumor tissues) with or without metastasis detected by IHC (magnification 200×). Positive IL-17A staining cells are indicated by red arrows. (B), Compared with HCC without metastasis (M-), the frequency of IL-17A positive cells was significantly higher in both tumor and non-tumor tissues in HCC with metastasis (M+). The frequency of IL-17A positive cells in tumor tissue was significantly higher than that in non-tumor tissue in HCCs with metastasis (M+). **, P<0.01; *, P<0.05. (C) and (D), Kaplan-Meier survival analysis showed that HCC patients with higher density of IL-17A positive cells had lower overall survival (C) and disease free survival rates (D).
Figure 2
Figure 2. RhIL-17A promoted HCC cell migration and invasion.
(A), Cell growth rate between PLC8024 cells treated with and without rhIL-17A (50 ng/mL) or TNF-α (10 ng/mL) was compared by XTT assay.**, P<0.01. (B), Representatives of foci formation in monolayer culture of PLC8024 cells treated with or without rhIL-17A (50 ng/mL) or TNF-α (10 ng/mL) for a week. (C), RhIL-17A treated HCC cells (PLC8024, QGY-7703 and MHCC-97L) showed higher motility in a wound-healing assay, compared with cells without RhIL-17A treatment. (D), Effect of RhIL-17A on cell invasion was detected by cell invasive assay. Representatives of cells migrated through Matrigel-coated transwell were shown in the left panel (magnification 100). Total invasive cell number in each chamber was summarized in the right panel. *, P<0.05.
Figure 3
Figure 3. RhIL-17A did not affect cell cytoskeleton and EMT.
(A), IF was used to detect F-actin distribution in PLC8024 cells treated with or without rhIL-17A (50 ng/mL) for 48 hr. (B), Western blot analysis was used to compare expression levels of epithelial markers (E-cadherin, α-catenin and β-catenin) and mesenchymal markers (fibronectin, Vimentin, N-cadherin and α-smooth muscle actin) in PLC8024 cells treated with or without rhIL-17A (50 ng/mL) for 48 hr. β–actin was used as a loading control.
Figure 4
Figure 4. RhIL-17A upregulated MMPs expression via activating NF-κB.
(A), Expressions of MMPs were compared by qPCR between cells treated with and without rhIL-17A (50 ng/mL) for 12 hours. *, P<0.05. (B), Expression of MMP9 was detected by western blot analysis in HCC cells treated with or without rhIL-17A (50 ng/mL) for 24 hours. (C), Western blot analysis was used to detect nuclear P-P65 (active form of NF-κB) expression in PLC8024 and MHCC-97L cells treated with rhIL-17A (50 ng/mL) at indicated time points. (D), Expressions of MMP2 and MMP9 were detected by qPCR in PLC8024 and MHCC-97L cells with different treatment. Control: without rhIL-17A treatment; IL-17A: treated with rhIL-17A (50 ng/mL); Helenalin: treated with helenalin (0.l µM) and rhIL-17A (50 ng/mL). *, P<0.05.
Figure 5
Figure 5. IL-17A correlated with MMP2 and MMP9 expression in HCC clinical samples.
Expression of IL-17A was positively associated with MMP2 (A) and MMP9 (B) expressions in 50 clinical HCC specimens. Analyzed with linear regression lines and pearson correlation by SPSS16.0.
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References (V体育官网)

    1. Semela D, Dufour JF. Angiogenesis and hepatocellular carcinoma. J Hepatol. 2004;41:864–880. - "VSports注册入口" PubMed
    1. Budhu A, Forgues M, Ye QH, Jia HL, He P, et al. Prediction of venous metastases, recurrence, and prognosis in hepatocellular carcinoma based on a unique immune response signature of the liver microenvironment. Cancer Cell. 2006;10:99–111. - PubMed
    1. Solinas G, Marchesi F, Garlanda C, Mantovani A, Allavena P. Inflammation-mediated promotion of invasion and metastasis. Cancer Metastasis Rev. 2010;29:243–248. - PubMed (VSports app下载)
    1. Condeelis J, Pollard JW. Macrophages: obligate partners for tumor cell migration, invasion, and metastasis. Cell. 2006;124:263–266. - "VSports app下载" PubMed
    1. Ikeguchi M, Oi K, Hirooka Y, Kaibara N. CD8+ lymphocyte infiltration and apoptosis in hepatocellular carcinoma. Eur J Surg Oncol. 2004;30:53–57. - PubMed

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