YB-1 transferred by gastric cancer exosomes promotes angiogenesis via enhancing the expression of angiogenic factors in
- PDF / 4,400,008 Bytes
- 12 Pages / 595.276 x 790.866 pts Page_size
- 34 Downloads / 170 Views
RESEARCH ARTICLE
Open Access
YB-1 transferred by gastric cancer exosomes promotes angiogenesis via enhancing the expression of angiogenic factors in vascular endothelial cells Xiaoxia Xue1, Jin Huang2, Kai Yu3, Xinyue Chen3, Yini He3, Dianjun Qi3 and Ying Wu3*
Abstract Background: Angiogenesis 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. Methods: In 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-NCExo), 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 GCderived exosomes were, separately, detected using PCR and Western blotting as well as RNA sequencing assays. Results: We 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 SGC7901-OE-Exo, although statistically higher mRNA of YB-1 was detected in the SGC-7901-OE-Exo. Conclusions: Our 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. Keywords: YB-1, Exosome, Gastric cancer, Angiogenesis, IL-8, VEGF, MMP-9, Ang-1
Background Gastric cancer (GC) is the third leading cause of cancer death around the world [1]. Most GC patients were * Correspondence: [email protected] 3 Department of General Practice, The First Hospital, China Medical University, 155 South Nanjing Street, Heping District, Shenyang 110001, Liaoning, China Full list of author information is available at the end of the article
diagnosed at late stage and showed unsatisfied response to traditional therapies, such as chemotherapy and radiotherapy [2, 3]. Angiogenesis is the necessary step for tumor progression; therefore antiangiogenic therapy has earned much attention [3–5]. However, GC patients seldomly benefit from existing antiangiogenesis agents, such as Apatinib and Ramucirumab [3, 6]. Thus, further
© The Author(s). 2020 Open Access This article is licensed u
Data Loading...
