机构:[a]Institute of Biomedical Engineering, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu,China[b]Radiation Therapy Center, Sichuan Cancer Hospital and Institute, Chengdu, China四川省肿瘤医院[c]Laboratory Animal Center, Sichuan University,Chengdu, China[d]Laboratory of Cardiovascular Diseases, Regenerative Medicine Research Center, West China Hospital, Sichuan University,Chengdu, China四川大学华西医院[e]Department of Biomedical Engineering, The City College of the City University of New York, New York, NY, USA
Although anti-angiogenic therapies (AATs) have some effects against multiple malignancies, they are limited by subsequent tumor vasculogenesis and progression. To investigate the mechanisms by which tumor vasculogenesis and progression following AATs, we transfected microRNA (miR)-9 into human umbilical vein endothelial cells (HUVECs) to mimic the tumor-associated endothelial cells in hepatocellular carcinoma and simulated the AATs in vitro and in vivo. We found that administration of the angiogenesis inhibitor vandetanib completely abolished miR-9-induced angiogenesis and promoted autophagy in HUVECs, but induced the release of vascular endothelial growth factor (VEGF)-enriched exosomes. These VEGF-enriched exosomes significantly promoted the formation of endothelial vessels and vasculogenic mimicry in hepatocellular carcinoma and its progression in mice. Anti-autophagic therapy is proposed to improve the efficacy of AATs. However, similar effects by AATs were observed with the application of anti-autophagy by 3-methyladenine. Our results revealed that tumor vasculogenesis and progression after AATs and anti-autophagic therapies were due to the cross-talk between endothelial and tumor cells via VEGF-enriched exosomes.
基金:
National Natural Science Foundation of ChinaNational Natural Science Foundation of China [11402153]; Excellent Young Scientist Foundation [2015SCU04A38]; Talent Introduction Scientific Research Projects Funded Start-Up Funds of Sichuan University [2082204174089]
第一作者机构:[a]Institute of Biomedical Engineering, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu,China[*a]Institute of Biomedical Engineering, West China School of Basic Sciences and Forensic Medicine, Sichuan University, No.17, Section 3, Renmin South Road, Chengdu, Sichuan 610041, P.R. China
通讯作者:
通讯机构:[a]Institute of Biomedical Engineering, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu,China[e]Department of Biomedical Engineering, The City College of the City University of New York, New York, NY, USA[*a]Institute of Biomedical Engineering, West China School of Basic Sciences and Forensic Medicine, Sichuan University, No.17, Section 3, Renmin South Road, Chengdu, Sichuan 610041, P.R. China[*b]Department of Biomedical Engineering, The City College of the City University of New York, 160 Convent Ave., New York, New York 10031, USA
推荐引用方式(GB/T 7714):
Ye Zeng,Xinghong Yao,Xiaoheng Liu,et al.Anti-angiogenesis triggers exosomes release from endothelial cells to promote tumor vasculogenesis[J].JOURNAL OF EXTRACELLULAR VESICLES.2019,8(1):doi:10.1080/20013078.2019.1629865.
APA:
Ye Zeng,Xinghong Yao,Xiaoheng Liu,Xueling He,Liang Li...&Bingmei M. Fu.(2019).Anti-angiogenesis triggers exosomes release from endothelial cells to promote tumor vasculogenesis.JOURNAL OF EXTRACELLULAR VESICLES,8,(1)
MLA:
Ye Zeng,et al."Anti-angiogenesis triggers exosomes release from endothelial cells to promote tumor vasculogenesis".JOURNAL OF EXTRACELLULAR VESICLES 8..1(2019)