Mesenchymal stem/stromal cells-derived IL-6 promotes nasopharyngeal carcinoma growth and resistance to cisplatin via upregulating CD73 expression
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
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-6 high CD73 high phenotype showed higher expression levels of gp80, gp130, p-STAT3, MMP-9 and -SMA, and clinically, a poorer prognosis than those with an IL-6 low CD73 low phenotype. We found that stimulation with conditioned media derived from IL-6 gene knocked out MSC (MSC IL6KO -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 IL6KO -CM were more sensitive to cisplatin than those co-cultured with MSC-CM. Additionally, MSC-derived IL-6 transcriptionally upregulated CD73 expression via activating STAT3 signaling pathway in NPC cells. In summary, our findings suggest that MSCs promote NPC progression and chemoresistance by upregulation of CD73 expression via activating STAT3 signaling pathway.