Enhanced IL-6/IL-6R signaling promotes growth and malignant properties in EBV-infected premalignant and cancerous nasopharyngeal epithelial cells.

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 impor...

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Autores principales: Guitao Zhang, Chi Man Tsang, Wen Deng, Yim Ling Yip, Vivian Wai-Yan Lui, Sze Chuen Cesar Wong, Annie Lai-Man Cheung, Pok Man Hau, Musheng Zeng, Maria Li Lung, Honglin Chen, Kwok Wai Lo, Kenzo Takada, Sai Wah Tsao
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Publicado: Public Library of Science (PLoS) 2013
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spelling oai:doaj.org-article:fffdc09df8444f2ca0cf90e6ebca3d8e2021-11-18T07:47:08ZEnhanced IL-6/IL-6R signaling promotes growth and malignant properties in EBV-infected premalignant and cancerous nasopharyngeal epithelial cells.1932-620310.1371/journal.pone.0062284https://doaj.org/article/fffdc09df8444f2ca0cf90e6ebca3d8e2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23658720/?tool=EBIhttps://doaj.org/toc/1932-6203Nasopharyngeal 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.Guitao ZhangChi Man TsangWen DengYim Ling YipVivian Wai-Yan LuiSze Chuen Cesar WongAnnie Lai-Man CheungPok Man HauMusheng ZengMaria Li LungHonglin ChenKwok Wai LoKenzo TakadaSai Wah TsaoPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 5, p e62284 (2013)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Guitao Zhang
Chi Man Tsang
Wen Deng
Yim Ling Yip
Vivian Wai-Yan Lui
Sze Chuen Cesar Wong
Annie Lai-Man Cheung
Pok Man Hau
Musheng Zeng
Maria Li Lung
Honglin Chen
Kwok Wai Lo
Kenzo Takada
Sai Wah Tsao
Enhanced IL-6/IL-6R signaling promotes growth and malignant properties in EBV-infected premalignant and cancerous nasopharyngeal epithelial cells.
description 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.
format article
author Guitao Zhang
Chi Man Tsang
Wen Deng
Yim Ling Yip
Vivian Wai-Yan Lui
Sze Chuen Cesar Wong
Annie Lai-Man Cheung
Pok Man Hau
Musheng Zeng
Maria Li Lung
Honglin Chen
Kwok Wai Lo
Kenzo Takada
Sai Wah Tsao
author_facet Guitao Zhang
Chi Man Tsang
Wen Deng
Yim Ling Yip
Vivian Wai-Yan Lui
Sze Chuen Cesar Wong
Annie Lai-Man Cheung
Pok Man Hau
Musheng Zeng
Maria Li Lung
Honglin Chen
Kwok Wai Lo
Kenzo Takada
Sai Wah Tsao
author_sort Guitao Zhang
title Enhanced IL-6/IL-6R signaling promotes growth and malignant properties in EBV-infected premalignant and cancerous nasopharyngeal epithelial cells.
title_short Enhanced IL-6/IL-6R signaling promotes growth and malignant properties in EBV-infected premalignant and cancerous nasopharyngeal epithelial cells.
title_full Enhanced IL-6/IL-6R signaling promotes growth and malignant properties in EBV-infected premalignant and cancerous nasopharyngeal epithelial cells.
title_fullStr Enhanced IL-6/IL-6R signaling promotes growth and malignant properties in EBV-infected premalignant and cancerous nasopharyngeal epithelial cells.
title_full_unstemmed Enhanced IL-6/IL-6R signaling promotes growth and malignant properties in EBV-infected premalignant and cancerous nasopharyngeal epithelial cells.
title_sort enhanced il-6/il-6r signaling promotes growth and malignant properties in ebv-infected premalignant and cancerous nasopharyngeal epithelial cells.
publisher Public Library of Science (PLoS)
publishDate 2013
url https://doaj.org/article/fffdc09df8444f2ca0cf90e6ebca3d8e
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