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Induction of CCL5 by Epstein-Barr virus infection enhances tumor angiogenesis in nasopharyngeal carcinoma.

Induction of CCL5 by Epstein-Barr virus infection enhances tumor angiogenesis in nasopharyngeal carcinoma.
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Ma W, Feng L, Zhang S, Zhang H, Zhang X, Qi X, Zhang Y, Feng Q, Xiang T, Zeng YX,


Ma W, Feng L, Zhang S, Zhang H, Zhang X, Qi X, Zhang Y, Feng Q, Xiang T, Zeng YX, (click to view)

Ma W, Feng L, Zhang S, Zhang H, Zhang X, Qi X, Zhang Y, Feng Q, Xiang T, Zeng YX,

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Cancer science 2018 03 23() doi 10.1111/cas.13584
Abstract

Nasopharyngeal carcinoma (NPC) is etiologically associated with Epstein-Barr virus (EBV) infection and is known to be highly vascularized. Previous studies have suggested that EBV oncoproteins contribute to NPC angiogenesis. However, the regulatory network of EBV in angiogenesis still remains elusive. Herein, we demonstrated a novel mechanism of EBV-induced angiogenesis in NPC. First, we showed that EBV-infected NPC cell lines generated larger tumors with more microvessels in mouse xenograft models. Subsequent proteomic analysis revealed that EBV infection increased the expression of a series of angiogenic factors, including chemokine (C-C motif) ligand 5 (CCL5). We then proved that CCL5 was a target of EBV in inducing tumor angiogenesis and growth. Further investigation through transcriptome analysis indicated that the proangiogenic function of CCL5 might be mediated by the PI3K/AKT pathway. Furthermore, we confirmed that activation of the PI3K/AKT and HIF-1α pathways was essential for CCL5-promoted angiogenesis. Finally, the immunohistochemical analysis of human NPC specimens also showed that CCL5 was correlated with angiogenesis. Taken together, our study identifies CCL5 as a key EBV-regulated molecular driver that promotes NPC angiogenesis, suggesting it as a potential therapeutic target. This article is protected by copyright. All rights reserved.

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