Exosomes derived from human mesenchymal stem cells promote gastric cancer cell growth and migration via the activation of the Akt pathway

被引:122
作者
Gu, Hongbing [1 ]
Ji, Runbi [1 ,2 ]
Zhang, Xu [2 ]
Wang, Mei [2 ]
Zhu, Wei [2 ]
Qian, Hui [2 ]
Chen, Yongchang [2 ]
Jiang, Pengcheng [3 ]
Xu, Wenrong [2 ]
机构
[1] Jiangsu Univ, Affiliated Peoples Hosp, Dept Lab Med, Zhenjiang 212002, Jiangsu, Peoples R China
[2] Jiangsu Univ, Sch Med, Jiangsu Key Lab Med Sci & Lab Med, 301 Xuefu Rd, Zhenjiang 212013, Jiangsu, Peoples R China
[3] Jiangsu Univ, Dept Gen Surg, Affiliated Peoples Hosp, 8 Dianli Rd, Zhenjiang 212002, Jiangsu, Peoples R China
基金
中国国家自然科学基金;
关键词
mesenchymal stem cells; exosomes; gastric cancer; epithelial-mesenchymal transition; Akt; TUMOR MICROENVIRONMENT; SIGNALING PATHWAY; RESISTANCE;
D O I
10.3892/mmr.2016.5625
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Mesenchymal stem cells (MSCs) are a component of the tumor microenvironment and can promote the development of gastric cancer through paracrine mechanism. However, the effects of MSC-exosomes (MSC-ex) on gastric cancer are less clear. The present study reported that MSC-ex promoted the proliferative and metastatic potential of gastric cancer cells ex vivo. It was found that MSC-ex enhanced the migration and invasion of HGC-27 cells via the induction of the epithelial-mesenchymal transition. MSC-ex increased the expression of mesenchymal markers and reduced the expression of epithelial markers in gastric cancer cells. MSC-ex also enhanced the tumorigenicity of gastric cancer cells ex vivo. MSC-ex induced the stemness of gastric cancer cells. The expression of octamer-binding transcription factor 4, ex determining region Y-box 2 and Lin28B significantly increased in gastric cancer cells treated with MSC-ex. The present study further demonstrated that MSC-ex elicited these biological effects predominantly via the activation of the protein kinase B signaling pathway. Taken together, the present findings provided novel evidence for the role of MSC-ex in gastric cancer and a new opportunity for improving the efficiency of gastric cancer treatment by targeting MSC-ex.
引用
收藏
页码:3452 / 3458
页数:7
相关论文
共 23 条
[1]   Tumor microenvironment: Bone marrow-mesenchymal stem cells as key players [J].
Barcellos-de-Souza, Pedro ;
Gori, Valentina ;
Bambi, Franco ;
Chiarugi, Paola .
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER, 2013, 1836 (02) :321-335
[2]   Bone marrow-derived mesenchymal stem cells and the tumor microenvironment [J].
Bergfeld, Scott A. ;
DeClerck, Yves A. .
CANCER AND METASTASIS REVIEWS, 2010, 29 (02) :249-261
[3]   Exosome Transfer from Stromal to Breast Cancer Cells Regulates Therapy Resistance Pathways [J].
Boelens, Mirjam C. ;
Wu, Tony J. ;
Nabet, Barzin Y. ;
Xu, Bihui ;
Qiu, Yu ;
Yoon, Taewon ;
Azzam, Diana J. ;
Victor, Christina Twyman-Saint ;
Wiemann, Brianne Z. ;
Ishwaran, Hemant ;
ter Brugge, Petra J. ;
Jonkers, Jos ;
Slingerland, Joyce ;
Minn, Andy J. .
CELL, 2014, 159 (03) :499-513
[4]   The mesenchymal tumor microenvironment A drug-resistant niche [J].
Cukierman, Edna ;
Bassi, Daniel E. .
CELL ADHESION & MIGRATION, 2012, 6 (03) :285-296
[5]   Nuclear PI3K signaling in cell growth and tumorigenesis [J].
Davis, William J. ;
Lehmann, Peter Z. ;
Li, Weimin .
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY, 2015, 3
[6]   Cancer Stem Cell-Like Phenotype and Survival Are Coordinately Regulated by Akt/FoxO/Bim Pathway [J].
Gargini, Ricardo ;
Cerliani, Juan P. ;
Escoll, Maribel ;
Anton, Ines M. ;
Wandosell, Francisco .
STEM CELLS, 2015, 33 (03) :646-660
[7]   Gastric Cancer Exosomes Trigger Differentiation of Umbilical Cord Derived Mesenchymal Stem Cells to Carcinoma-Associated Fibroblasts through TGF-β/Smad Pathway [J].
Gu, Jianmei ;
Qian, Hui ;
Shen, Li ;
Zhang, Xu ;
Zhu, Wei ;
Huang, Ling ;
Yan, Yongmin ;
Mao, Fei ;
Zhao, Chonghui ;
Shi, Yunyan ;
Xu, Wenrong .
PLOS ONE, 2012, 7 (12)
[8]   Exosomes Released by Melanoma Cells Prepare Sentinel Lymph Nodes for Tumor Metastasis [J].
Hood, Joshua L. ;
Roman, Susana San ;
Wickline, Samuel A. .
CANCER RESEARCH, 2011, 71 (11) :3792-3801
[9]   Exosomes derived from human mesenchymal stem cells confer drug resistance in gastric cancer [J].
Ji, Runbi ;
Zhang, Bin ;
Zhang, Xu ;
Xue, Jianguo ;
Yuan, Xiao ;
Yan, Yongmin ;
Wang, Mei ;
Zhu, Wei ;
Qian, Hui ;
Xu, Wenrong .
CELL CYCLE, 2015, 14 (15) :2473-2483
[10]  
Lee JK, 2013, PLOS ONE, V8, DOI [10.1371/journal.pone.0084256, 10.1371/journal.pone.0066555]