Mesenchymal Stem/stromal Cells-derived IL-6 Promotes Nasopharyngeal Carcinoma Growth and Resistance to Cisplatin Via Upregulating CD73 Expression

Overview

Journal J Cancer

Specialty Oncology

Date 2020 Mar 5

PMID 32127934

Citations 24

Authors

Jincheng Zeng

Shasha Chen

Caihong Li

Ziyu Ye

Bihua Lin

Yanfang Liang

Bin Wang

Yan Ma

Xingxing Chai

Xin Zhang

Keyuan Zhou

Qunzhou Zhang

Haitao Zhang

Affiliations

Soon will be listed here.

Abstract

Previous studies have implicated the important role of mesenchymal stem/stromal cells (MSCs) within tumor microenvironment (TME) in the pathogenesis and progression of nasopharyngeal carcinoma (NPC), but the potential mechanisms are still unclear. Herein, we showed that an elevated IL-6 level was positively correlated with elevated expression of CD73 in TME of NPC. NPC specimens with an IL-6CD73 phenotype showed higher expression levels of gp80, gp130, p-STAT3, MMP-9 and α-SMA, and clinically, a poorer prognosis than those with an IL-6CD73 phenotype. We found that stimulation with conditioned media derived from IL-6 gene knocked out MSC (MSC-CM) down-regulated the expression of CD73, IL-6, gp80, p-STAT3, and proliferative cell nuclear antigen (PCNA) in CNE-2 NPC cells. Meanwhile, NPC cells co-cultured with MSC-CM were more sensitive to cisplatin than those co-cultured with MSC-CM. Additionally, MSC-derived IL-6 transcriptionally upregulated CD73 expression activating STAT3 signaling pathway in NPC cells. In summary, our findings suggest that MSCs promote NPC progression and chemoresistance by upregulation of CD73 expression activating STAT3 signaling pathway.

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