YB-1 transferred by gastric cancer exosomes promotes angiogenesis via enhancing the expression of angiogenic factors in vascular endothelial cells

BMC Cancer

Ying Wu¹  Kai Yu¹  Dianjun Qi¹  Xinyue Chen¹  Yini He¹  Jin Huang²  Xiaoxia Xue³ 

[1] Department of General Practice, The First Hospital, China Medical University, 155 South Nanjing Street, Heping District, 110001, Shenyang, Liaoning, China;Department of Radiation Therapy, The First Hospital, China Medical University, 518 Chuangxin Road, Hunnan District, 110167, Shenyang, Liaoning, China;Science Experiment Center, China Medical University, 77 Puhe Road, Shenyang North New Area, 110122, Shenyang, Liaoning, China;

关键词: YB-1;    Exosome;    Gastric cancer;    Angiogenesis;    IL-8;    VEGF;    MMP-9;    Ang-1;   

DOI  :  10.1186/s12885-020-07509-6

来源: Springer

【 摘 要 】

BackgroundAngiogenesis is important for the progression of gastric cancer (GC). Y-box binding protein 1 (YB-1) predicts advanced disease and indicates neovasculature formation in GC tissues, while the related mechanisms remain elusive. Exosomes mediate intercellular communications via transferring various molecules including proteins, lipids, mRNAs, and microRNAs, while the cargos of GC exosomes and the related mechanisms in GC angiogenesis were rarely reported except for several microRNAs.MethodsIn this study, human umbilical vein endothelial cells (HUVECs) were, respectively, treated by the exosomes isolated from the YB-1 transfected and the control SGC-7901 cells (SGC-7901-OE-Exo and SGC-7901-NC-Exo), and their apoptosis, proliferation, migration, invasion, and angiogenesis were, sequentially, compared. The levels of angiogenic factors including VEGF, Ang-1, MMP-9 and IL-8 in the exosome-treated HUVECs and the GC-derived exosomes were, separately, detected using PCR and Western blotting as well as RNA sequencing assays.ResultsWe observed the consistent level of YB-1 in the exosomes and their originated GC cells, and the internalization of exosomes into HUVECs. Comparing with SGC-7901-NC-Exo, SGC-7901-OE-Exo significantly inhibited the apoptosis but promoted the proliferation, migration, invasion, and angiogenesis of HUVECs, within which the increased mRNA and protein levels of VEGF, Ang-1, MMP-9 and IL-8 were demonstrated. Meanwhile, mRNA levels of VEGF, Ang-1, MMP-9 and IL-8 showed no significant difference between SGC-7901-NC-Exo and SGC-7901-OE-Exo, although statistically higher mRNA of YB-1 was detected in the SGC-7901-OE-Exo.ConclusionsOur findings illustrate YB-1 as the key component of exosome to promote GC angiogenesis by upregulating specific angiogenic factors in the exosome-treated endothelial cells but not in the exosomes themselves.

【 授权许可】

CC BY