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

D Liu, R Zhang, J Wu, Y Pu, X Yin… - Oncology …, 2017 - spandidos-publications.com
D Liu, R Zhang, J Wu, Y Pu, X Yin, Y Cheng, J Wu, C Feng, Y Luo, J Zhang
Oncology Reports, 2017spandidos-publications.com
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 …
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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