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posted on 2023-03-31, 00:47 authored by Di Huang, Shi-Jian Song, Zi-Zhao Wu, Wei Wu, Xiu-Ying Cui, Jia-Ning Chen, Mu-Sheng Zeng, Shi-Cheng Su Figure S6 related to Figure 6. The interaction between EBV+NPC cells and macrophages promotes metastasis in a humanized mouse model.
Funding
Natural Science Foundation of China
National Key Research and Development Program of China
Science Foundation of Guangdong Province
China Postdoctoral Science Foundation
Guangzhou Science and Technology
Translational medicine public platform of Guangdong Province
Scientific and Technical Innovative Youth Talents of Guangdong
Guangdong Department of Science & Technology Translational Medicine Center
Sun Yat-sen University
History
ARTICLE ABSTRACT
Chronic inflammation induced by persistent microbial infection plays an essential role in tumor progression. Although it is well documented that Epstein–Barr virus (EBV) infection is closely associated with nasopharyngeal carcinoma (NPC), how EBV-induced inflammation promotes NPC progression remains largely unknown. Here, we report that tumor infiltration of tumor-associated macrophages (TAM) and expression of CCL18, the cytokine preferentially secreted by TAM, closely correlate with serum EBV infection titers and tumor progression in two cohorts of NPC patients. In vitro, compared with EBV− NPC cell lines, EBV+ NPC cell lines exhibited superior capacity to attract monocytes and skew them to differentiate to a TAM-like phenotype. Cytokine profiling analysis revealed that NPC cells with active EBV replications recruited monocytes by VEGF and induced TAM by GM-CSF in an NF-κB–dependent manner. Reciprocally, TAM induced epithelial–mesenchymal transition and furthered NF-κB activation of tumor cells by CCL18. In humanized mice, NPC cells with active EBV replications exhibited increased metastasis, and neutralization of CCL18, GM-CSF, and VEGF significantly reduced metastasis. Collectively, our work defines a feed-forward loop between tumor cells and macrophages in NPC, which shows how metastatic potential can evolve concurrently with virus-induced chronic inflammation. Cancer Res; 77(13); 3591–604. ©2017 AACR.
