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Neurotensin/IL-8 pathway orchestrates local inflammatory response and tumor invasion by inducing M2 polarization of Tumor-Associated macrophages and epithelial-mesenchymal transition of hepatocellular carcinoma cells

文献类型：期刊论文

作者Xiao, Pei2,3; Long, Xinxin4; Zhang, Lijie2,3; Ye, Yingnan2; Guo, Jincheng1,5; Liu, Pengpeng2; Zhang, Rui2; Ning, Junya2,3; Yu, Wenwen3; Wei, Feng3
刊名ONCOIMMUNOLOGY
出版日期2018
卷号7期号:7页码:19
关键词Neurotensin interleukin-8 hepatocellular carcinoma epithelial-mesenchymal transition tumor-associated macrophages
ISSN号2162-402X
DOI10.1080/2162402X.2018.1440166
英文摘要We previously demonstrated that neurotensin (NTS) induces local inflammation and promotes tumor invasion in hepatocellular carcinoma (HCC). However, the underlying molecular mechanisms are not clear. In this study, positive correlations between NTS and interleukin (IL)-8 were identified at both the mRNA and protein levels in 71 fresh HCC tissues and 100 paraffin-embedded HCC tissues. Furthermore, significant correlations were determined among the co-expression of NTS and IL-8, infiltration of inflammatory cells and enhanced epithelial-mesenchymal transition (EMT) of HCC cells. NTS-induced IL-8 production was associated with activation of the mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-B) pathways rather than the protein kinase C (PKC) and phosphoinositide-3 kinase (PI3K) pathways, whose specific antagonists significantly inhibited activation of the NTS/IL-8 pathway. IL-8, which promoted EMT and HCC invasion both in vitro and in vivo, was produced by NTS-induced HCC cells and was effectively attenuated by blocking IL-8 receptors in vitro. Moreover, HCC-derived IL-8 attracted more CD68(+) tumor-associated macrophages (TAMs) and CD66b(+) polymorphonuclear neutrophils (PMNs) to the local microenvironment, displaying enhanced cytokine secretion and phagocytosis. IL-8 stimulated the M2 polarization of TAMs, which promoted the EMT and invasive potential of HCC cells. Blockage of the IL-8 receptor, NTR1 receptor or both significantly reduced HCC metastases in tumor-bearing mouse models via inhibiting EMT. In summary, aberrant activation of the NTS/IL-8 pathway in HCC dramatically stimulated the invasive potential of HCC cells. HCC-derived IL-8 promoted a pro-oncogenic inflammatory microenvironment by inducing M2-type TAMs and indirectly promoting EMT, which might be a valuable therapeutic target to prevent tumor progression.
资助项目National Natural Science Foundation of China[81472473] ; National Natural Science Foundation of China[81272360] ; National Key Scientific and Technological Project of China[2015BAI12B12] ; National Key Scientific and Technological Project of China[2015BAI12B15] ; Scientific and Technological Project of Tianjin, China[13ZCZCSY20300] ; Key Project of Tianjin Health and Family Planning Commission[16KG126]
WOS研究方向Oncology ; Immunology
语种英语
WOS记录号WOS:000433549100005
出版者TAYLOR & FRANCIS INC
源URL[http://119.78.100.204/handle/2XEOYT63/5243]  
专题中国科学院计算技术研究所期刊论文_英文
通讯作者Yu, Jinpu
作者单位1.Chinese Acad Sci, Inst Comp Technol, Bioinformat Res Grp, Beijing, Peoples R China
2.Tianjin Med Univ Canc Inst & Hosp, Canc Mol Diagnost Core, Key Lab Canc Prevent & Therapy, Natl Clin Res Ctr Caner, Tianjin, Peoples R China
3.Tianjin Med Univ Canc Inst & Hosp, Dept Immunol, Natl Clin Res Ctr Caner, Key Lab Canc Immunol & Biotherapy, Tianjin, Peoples R China
4.Tengzhou Cent Peoples Hosp, Dept Oncol, Tengzhou, Shandong, Peoples R China
5.Chinese Acad Sci, Inst Comp Technol, Hlth Big Data, Beijing, Peoples R China
推荐引用方式
GB/T 7714		 Xiao, Pei,Long, Xinxin,Zhang, Lijie,et al. Neurotensin/IL-8 pathway orchestrates local inflammatory response and tumor invasion by inducing M2 polarization of Tumor-Associated macrophages and epithelial-mesenchymal transition of hepatocellular carcinoma cells[J]. ONCOIMMUNOLOGY,2018,7(7):19.
APA Xiao, Pei.,Long, Xinxin.,Zhang, Lijie.,Ye, Yingnan.,Guo, Jincheng.,...&Yu, Jinpu.(2018).Neurotensin/IL-8 pathway orchestrates local inflammatory response and tumor invasion by inducing M2 polarization of Tumor-Associated macrophages and epithelial-mesenchymal transition of hepatocellular carcinoma cells.ONCOIMMUNOLOGY,7(7),19.
MLA Xiao, Pei,et al."Neurotensin/IL-8 pathway orchestrates local inflammatory response and tumor invasion by inducing M2 polarization of Tumor-Associated macrophages and epithelial-mesenchymal transition of hepatocellular carcinoma cells".ONCOIMMUNOLOGY 7.7(2018):19.

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来源：计算技术研究所

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