Exosomes Derived from Irradiated Esophageal Carcinoma-Infiltrating T Cells Promote Metastasis by Inducing the Epithelial-Mesenchymal Transition in Esophageal Cancer Cells

被引:55
作者
Min, Hua [1 ]
Sun, Xiangdong [2 ]
Yang, Xi [1 ]
Zhu, Hongcheng [1 ]
Liu, Jia [1 ]
Wang, Yuandong [1 ]
Chen, Guangzong [1 ]
Sun, Xinchen [1 ]
机构
[1] Nanjing Med Univ, Dept Radiotherapy, Affiliated Hosp 1, Nanjing 210000, Jiangsu, Peoples R China
[2] PLA, Dept Radiotherapy, Hosp 81, Nanjing 210000, Jiangsu, Peoples R China
关键词
T cells; Radiotherapy; Exosome; Esophageal carcinoma; Epithelial-mesenchymal transition; Metastasis; PROTEOMIC ANALYSIS; VASCULOGENIC MIMICRY; MULTIVESICULAR BODY; GRANULES; LYMPHOCYTES; ACTIVATION; MECHANISMS; EXPRESSION; TWIST1; EMT;
D O I
10.1007/s12253-016-0185-z
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Exosomes are nanovesicles derived from tumor and normal cells that are detectable in human biological fluids, such as plasma, and cell culture supernatants. The function of exosome secretion from "normal" cells is unclear. Although numerous studies have investigated exosomes derived from hematopoietic cells, little is known regarding exosomes fromT cells, even though these cells play significant roles in innate and acquired immunity. A CCK-8 assay was used to examine the ability of exosomes to inhibit TE13 cell proliferation. In vitro invasion and wound healing assays were conducted to explore the effects of exosomes on TE13 cell migration and invasion. A Western blottinganalys is was performed to investigate the effects of exosomes on the expression of the EMT-related molecules beta-catenin, NF-kappa B and snail. This study aimed to investigate the effects of exosomes from irradiated T cells on the human esophageal squamous cell carcinoma (ESCC) cell line TE13 and revealed that exosomes inhibit the proliferation but promote the metastasis of TE13 cells in a dose-and time-dependent manner. Furthermore, exosomes significantly increased the expression of beta-catenin, NF-kappa B and snail in TE13 cells. The results of this study suggest an important role for T cell-derived exosomes in the progression of esophageal carcinoma: T cell-derived exosomes promote esophageal cancer metastasis, likely by promoting the EMT through the upregulation of beta-catenin and the NF-kappa B/snail pathway. Moreover, this study supports the use of exosomes as a nearly perfect example of biomimetic nanovesicles that could be utilized in future therapeutic strategies against various diseases, including cancer.
引用
收藏
页码:11 / 18
页数:8
相关论文
共 58 条
[1]   Ionizing Radiation and Glioblastoma Exosomes: Implications in Tumor Biology and Cell Migration [J].
Arscott, W. Tris ;
Tandle, Anita T. ;
Zhao, Shuping ;
Shabason, Jacob E. ;
Gordon, Ira K. ;
Schlaff, Cody D. ;
Zhang, Guofeng ;
Tofilon, Philip J. ;
Camphausen, Kevin A. .
TRANSLATIONAL ONCOLOGY, 2013, 6 (06) :638-U254
[2]   Molecular mechanisms controlling E-cadherin expression in breast cancer [J].
Baranwal, Somesh ;
Alahari, Suresh K. .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2009, 384 (01) :6-11
[3]   Proteomic analysis of exosomes isolated from human malignant pleural effusions [J].
Bard, MP ;
Hegmans, JP ;
Hemmes, A ;
Luider, TM ;
Willemsen, R ;
Severijnen, LAA ;
van Meerbeeck, JP ;
Burgers, SA ;
Hoogsteden, HC ;
Lambrecht, BN .
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 2004, 31 (01) :114-121
[4]   β-catenin:: A pivot between cell adhesion and Wnt signalling [J].
Bienz, M .
CURRENT BIOLOGY, 2005, 15 (02) :R64-R67
[5]   Comparative proteomics of exosomes secreted by tumoral Jurkat T cells and normal human T cell blasts unravels a potential tumorigenic role for valosin-containing protein [J].
Bosque, Alberto ;
Dietz, Lisa ;
Gallego-Lleyda, Ana ;
Sanclemente, Manuel ;
Iturralde, Maria ;
Naval, Javier ;
Alava, Maria Angeles ;
Martinez-Lostao, Luis ;
Thierse, Hermann-Josef ;
Anel, Alberto .
ONCOTARGET, 2016, 7 (20) :29287-29305
[6]   Activated T Cell Exosomes Promote Tumor Invasion via Fas Signaling Pathway [J].
Cai, Zhijian ;
Yang, Fei ;
Yu, Lei ;
Yu, Zhou ;
Jiang, Lingling ;
Wang, Qingqing ;
Yang, Yunshan ;
Wang, Lie ;
Cao, Xuetao ;
Wang, Jianli .
JOURNAL OF IMMUNOLOGY, 2012, 188 (12) :5954-5961
[7]   Endostatin combined with radiotherapy suppresses vasculogenic mimicry formation through inhibition of epithelial-mesenchymal transition in esophageal cancer [J].
Chen, Xiaochen ;
Zhang, Hao ;
Zhu, Hongcheng ;
Yang, Xi ;
Yang, Yuehua ;
Yang, Yan ;
Min, Hua ;
Chen, Guangzong ;
Liu, Jia ;
Lu, Jing ;
Cheng, Hongyan ;
Sun, Xinchen .
TUMOR BIOLOGY, 2016, 37 (04) :4679-4688
[8]   Biogenesis, Secretion, and Intercellular Interactions of Exosomes and Other Extracellular Vesicles [J].
Colombo, Marina ;
Raposo, Graca ;
Thery, Clotilde .
ANNUAL REVIEW OF CELL AND DEVELOPMENTAL BIOLOGY, VOL 30, 2014, 30 :255-289
[9]   Current management of esophageal cancer [J].
D'Journo, Xavier Benoit ;
Thomas, Pascal Alexandre .
JOURNAL OF THORACIC DISEASE, 2014, 6 :S253-S264
[10]   Ionizing radiation inhibition of distant untreated tumors (abscopal effect) is immune mediated [J].
Demaria, S ;
Ng, B ;
Devitt, ML ;
Babb, JS ;
Kawashima, N ;
Liebes, L ;
Formenti, SC .
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 2004, 58 (03) :862-870