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).
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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Item Type: |
Article
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Status: |
Published |
Creators/Authors: |
Creators | Email | Pitt Username | ORCID ![](/images/orcid_id_24x24.png) |
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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 | | | |
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Contributors: |
Contribution | Contributors Name | Email | Pitt Username | ORCID ![](/images/orcid_id_24x24.png) |
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Editor | Tao, Qian | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED |
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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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