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Anti-angiogenesis triggers exosomes release from endothelial cells to promote tumor vasculogenesis

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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 [c]Laboratory Animal Center, Sichuan University,Chengdu, China [d]Laboratory of Cardiovascular Diseases, Regenerative Medicine Research Center, West China Hospital, Sichuan University,Chengdu, China [e]Department of Biomedical Engineering, The City College of the City University of New York, New York, NY, USA
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关键词: Exosomes vascular endothelial growth factor (VEGF) anti-angiogenesis anti-autophagy pre-metastatic niches

摘要:
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.

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出版当年[2019]版:
大类 | 2 区 医学
小类 | 2 区 细胞生物学
最新[2023]版:
大类 | 1 区 医学
小类 | 2 区 细胞生物学
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出版当年[2019]版:
Q1 CELL BIOLOGY
最新[2023]版:
Q1 CELL BIOLOGY

影响因子: 最新[2023版] 最新五年平均 出版当年[2019版] 出版当年五年平均 出版前一年[2018版] 出版后一年[2020版]

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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
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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
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