Interleukin 17A promotes gastric cancer invasiveness via NF-κB mediated matrix metalloproteinases 2 and 9 expression

Yidong Wang; Hong Wu; Xiaoling Wu; Zhuoqiong Bian; Qing Gao

doi:10.1371/journal.pone.0096678

Interleukin 17A promotes gastric cancer invasiveness via NF-κB mediated matrix metalloproteinases 2 and 9 expression

PLoS One. 2014 Jun 6;9(6):e96678. doi: 10.1371/journal.pone.0096678. eCollection 2014.

Authors

Yidong Wang¹, Hong Wu², Xiaoling Wu¹, Zhuoqiong Bian³, Qing Gao¹

Affiliations

¹ Department of Obstetrics and Gynecology, the Second Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi, P. R. China.
² Department of General Surgery, XIAN XD GROUP Hospital, Xi'an, Shaanxi, P. R. China.
³ Department 5 of rheumatology, the fifth hospital of Xi'an city, Xi'an, Shaanxi, P. R. China.

Abstract

Interleukin 17A (IL-17A), as a pro-inflammatory cytokine, is involved in pathology of inflammatory diseases and tumor microenvironment. The aim of this study is to investigate the effect of IL-17A on the invasiveness of gastric cancer (GC). In the study, we found that IL-17A could promote the migration and invasion of GC cells. Furthermore, after treated with IL-17A, the expressions and activities of matrix metalloproteinase 2 (MMP-2) and MMP-9 were upregulated, while the expressions of TIMP-1 and TIMP-2 were downregulated. Moreover, the nuclear/overall fractions of p65 and p50 were dramatically elevated by IL-17A. Pretreatment with helenalin, a nuclear factor-κB (NF-κB) inhibitor, was proved to abolish the promoting effect of IL-17A on the invasion ability of GC cells and upregulation of MMP-2 and MMP-9. In conclusion, our findings illustrated that IL-17A could promote the invasion of GC cells by activating NF-κB pathway, and subsequently upregulating the expression of MMP-2 and MMP-9. These results may lead to the identification of new diagnostic markers and therapeutic targets of GC.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Line, Tumor
Cell Movement / drug effects
Gene Expression Regulation, Neoplastic
Humans
Interleukin-17 / pharmacology*
Matrix Metalloproteinase 2 / genetics
Matrix Metalloproteinase 2 / metabolism
Matrix Metalloproteinase 9 / genetics
Matrix Metalloproteinase 9 / metabolism*
NF-kappa B / genetics
NF-kappa B / metabolism
Neoplasm Invasiveness
Stomach Neoplasms / metabolism*
Tissue Inhibitor of Metalloproteinase-1 / genetics
Tissue Inhibitor of Metalloproteinase-1 / metabolism
Tissue Inhibitor of Metalloproteinase-2 / genetics
Tissue Inhibitor of Metalloproteinase-2 / metabolism

Substances

Interleukin-17
NF-kappa B
Tissue Inhibitor of Metalloproteinase-1
Tissue Inhibitor of Metalloproteinase-2
MMP2 protein, human
Matrix Metalloproteinase 2
MMP9 protein, human
Matrix Metalloproteinase 9

Grants and funding

The project was supported by National Natural Science Foundation of China (No. 81070536) and Youth Scientific Funds of The Central Hospital of Taian (2011ZRQNO35). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.