Interleukin-17A promotes esophageal adenocarcinoma cell invasiveness through ROS-dependent, NF-κB-mediated MMP-2/9 activation

  • Authors:
    • Dong Liu
    • Rong Zhang
    • Jie Wu
    • Yansong Pu
    • Xiaoran Yin
    • Yan Cheng
    • Jing Wu
    • Cheng Feng
    • Yumei Luo
    • Jun Zhang
  • View Affiliations

  • Published online on: February 7, 2017     https://doi.org/10.3892/or.2017.5426
  • Pages: 1779-1785
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Abstract

Interleukin-17A (IL-17A), a pro-inflammatory cytokine secreted primarily by Th17 cells, has been proved to be involved in the microenvironment of certain inflammation-related tumors. However, the role of IL-17A in cancer development has always been controversial. In this study, we investigated the effect of IL-17A on the regulation of esophageal adenocarcinoma (EAC) cell invasiveness and related molecular mechanism. Surface IL-17 receptor (IL-17R) expression on human EAC cell line OE19 was examined using flow cytometry. The effect of IL-17A on cell proliferation was measured by MTT assay. Cell migration and invasive ability in vitro were assessed by wound-healing and Matrigel-coated Transwell invasion assay. Intracellular reactive oxygen species (ROS) levels were determined by flow cytometry and fluorescence microscope. The protein expression levels of MMP-2, MMP-9, NF-κB and p-IκB-α were detected by western blotting. Our results showed that IL-17A promoted migration and invasion of OE19 cells in a dose-dependent manner, however it had less effect on OE19 cell proliferation. Furthermore, IL-17A treatment significantly upregulated the expression of MMP-2 and MMP-9, stimulated intracellular ROS production, increased IκB-α phosphorylation and NF-κB nuclear translocation. Nevertheless, IL-17A-induced expression of MMP-2/9 and OE19 cell invasiveness were both inhibited by pretreatment with N-acetyl-L-cysteine (NAC, a ROS scavenger) or pyrrolidine dithiocarbamate (PDTC, a NF-κB inhibitor). In conclusion, these findings demonstrate that IL-17A can promote the migration and invasiveness of EAC cells through ROS/NF-κB/MMP-2/9 signaling pathway activation, indicating that IL-17A may be a potential therapeutic target for EAC.
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March-2017
Volume 37 Issue 3

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Liu D, Zhang R, Wu J, Pu Y, Yin X, Cheng Y, Wu J, Feng C, Luo Y, Zhang J, Zhang J, et al: Interleukin-17A promotes esophageal adenocarcinoma cell invasiveness through ROS-dependent, NF-κB-mediated MMP-2/9 activation. Oncol Rep 37: 1779-1785, 2017.
APA
Liu, D., Zhang, R., Wu, J., Pu, Y., Yin, X., Cheng, Y. ... Zhang, J. (2017). Interleukin-17A promotes esophageal adenocarcinoma cell invasiveness through ROS-dependent, NF-κB-mediated MMP-2/9 activation. Oncology Reports, 37, 1779-1785. https://doi.org/10.3892/or.2017.5426
MLA
Liu, D., Zhang, R., Wu, J., Pu, Y., Yin, X., Cheng, Y., Wu, J., Feng, C., Luo, Y., Zhang, J."Interleukin-17A promotes esophageal adenocarcinoma cell invasiveness through ROS-dependent, NF-κB-mediated MMP-2/9 activation". Oncology Reports 37.3 (2017): 1779-1785.
Chicago
Liu, D., Zhang, R., Wu, J., Pu, Y., Yin, X., Cheng, Y., Wu, J., Feng, C., Luo, Y., Zhang, J."Interleukin-17A promotes esophageal adenocarcinoma cell invasiveness through ROS-dependent, NF-κB-mediated MMP-2/9 activation". Oncology Reports 37, no. 3 (2017): 1779-1785. https://doi.org/10.3892/or.2017.5426