Abstract
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.
Highlights
Angiogenesis is important for the progression of gastric cancer (GC)
human umbilical vein endothelial cells (HUVECs) were purchased from the Sciencell and cultured in ECM consisting of 500 ml of basal medium, 25 ml of fetal bovine serum, 5 ml of endothelial cell growth supplement (ECGS) and 5 ml of penicillin/ streptomycin solution (P/S)
Identification of Y-box binding protein 1 (YB-1) expression in GC-derived exosomes Based on the observations of electron microscope and western blot assays, it is identified that the exosomes were derived successfully from GC cells according to the consistent shape and size with the previous descriptions (30-110 nm sized vesicles) and the expression of exosome markers including CD9 and Hsp70 (Fig. 1a, b and d)
Summary
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. Gastric cancer (GC) is the third leading cause of cancer death around the world [1]. Studies for angiogenesis have focused on the intercellular communications, with exosomes as the important mediators [7, 8]. Y-box binding protein-1 (YB-1) has been reported the important component of inactive messenger RNA particles (mRNPs), which are the form of stabilized mRNAs transferred by exosomes during cellular communications [12]. Nontheless, the existence of YB-1 in exosomes and the roles for cancer angiogenesis are still uncovered
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