LMP1‐positive extracellular vesicles promote radioresistance in nasopharyngeal carcinoma cells through P38 MAPK signaling. (22nd August 2019)

• Record Type: Journal Article
• Authors: Zhang, Zhibao; Yu, Xuehui; Zhou, Zhuan; Li, Bo; Peng, Jinwu; Wu, Xia; Luo, Xiangjian; Yang, Lifang
• Is Part Of: Cancer medicine. Volume 8:Number 13(2019:Oct.)
• Page Start: 6082
• Page End: 6094
• Publication Date: 2019-08-22
• Subjects: extracellular vesicle -- LMP1 -- nasopharyngeal carcinoma -- P38 -- radioresistance; 616.994005
• DOI: 10.1002/cam4.2506
• Languages: English
• ISSNs: 2045-7634

Abstract

Abstract: Radioresistance has been one of the impediments to effective nasopharyngeal carcinoma (NPC) therapy in clinical settings. Epstein‐Barr virus (EBV) encoded latent membrane protein 1 (LMP1) is expressed in NPC and has potent effects on radioresistance. It has been detected in extracellular vesicles (EVs) or exosomes and shown to promote tumor proliferation and invasive potential. However, whether LMP1‐positive EVs can confer radioresistance to cancer cells and the mechanism used to promote radioresistance need to be elucidated. In this study, the data showed that EVs derived from LMP1‐positive NPC cells could induce recipient NPC cell proliferation and invasion and suppress apoptosis, especially promoting radioresistance. In addition, LMP1 could increase the secretion of LMP1‐positive EVs. Furthermore, transmitted LMP1 subsequently performed its oncogenic functions through activating P38 MAPK signaling in recipient cells, and inhibiting P38 activity could efficaciously restore the sensitivity of NPC cells to ionizing radiation (IR). Finally, we found that LMP1‐positive EVs could promote tumor growth and P38 inhibition eliminates this promoting effect in vivo, and EV formation is associated with a poor prognosis in NPC patients. These results showed that a few cells expressing LMP1 could enhance the radioresistance of NPC cells through potentially impacting the infected host and also modulating the tumor microenvironment. Abstract : In present study, we mainly demonstrated a new mechanism underlying NPC radioresistance that mediated by EBV‐LMP1‐positive EVs through P38 MAPK signaling. And the results showed that a few number of cells expressing LMP1 could enhance the radioresistance of NPC cells through both potentially impacting the infected host and also modulating the tumor microenvironment through the EVs.