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Enhanced IL-6/IL-6R Signaling Promotes Growth and Malignant Properties in EBV-Infected Premalignant and Cancerous Nasopharyngeal Epithelial Cells

Zhang, G and Tsang, CM and Deng, W and Yip, YL and Lui, VWY and Wong, SCC and Cheung, ALM and Hau, PM and Zeng, M and Lung, ML and Chen, H and Lo, KW and Takada, K and Tsao, SW (2013) Enhanced IL-6/IL-6R Signaling Promotes Growth and Malignant Properties in EBV-Infected Premalignant and Cancerous Nasopharyngeal Epithelial Cells. PLoS ONE, 8 (5).

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Abstract

Nasopharyngeal carcinoma (NPC) is etiologically associated with Epstein-Barr virus (EBV) infection. However, the exact role of EBV in NPC pathogenesis remains elusive. Activation of signal transducer and activator of transcription 3 (STAT3) is common in human cancers including NPC and plays an important role in the pathogenesis and progression of human cancers. Interleukin-6 (IL-6), a major inflammatory cytokine, is a potent activator of STAT3. In this study, we report that EBV-infected immortalized nasopharyngeal epithelial (NPE) cells often acquire an enhanced response to IL-6-induced STAT3 activation to promote their growth and invasive properties. Interestingly, this enhanced IL-6/STAT3 response was mediated by overexpression of IL-6 receptor (IL-6R). Furthermore, IL-6R overexpression enhanced IL-6-induced STAT3 activation in uninfected immortalized NPE cells in vitro, and promoted growth and tumorigenicity of EBV-positive NPC cell line (C666-1) in vivo. Moreover, it is shown for the first time that IL-6R was overexpressed in clinical specimens of NPC. IL-6 expression could also be strongly detected in the stromal cells of NPC and a higher circulating level of IL-6 was found in the sera of advance-staged NPC patients compared to the control subjects. Therefore, IL-6R overexpression, coupled with enhanced IL-6/STAT3 signaling may facilitate the malignant transformation of EBV-infected premalignant NPE cells into cancer cells, and enhance malignant properties of NPC cells. © 2013 Zhang et al.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Zhang, G
Tsang, CM
Deng, W
Yip, YL
Lui, VWY
Wong, SCC
Cheung, ALM
Hau, PM
Zeng, M
Lung, ML
Chen, H
Lo, KW
Takada, K
Tsao, SW
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorTao, QianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Date: 1 May 2013
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 8
Number: 5
DOI or Unique Handle: 10.1371/journal.pone.0062284
Schools and Programs: School of Medicine > Otolaryngology
Refereed: Yes
Date Deposited: 14 May 2013 16:09
Last Modified: 13 Oct 2017 22:57
URI: http://d-scholarship.pitt.edu/id/eprint/18671

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