Exosomes derived from HeLa cells break down vascular integrity by triggering endoplasmic reticulum stress in endothelial cells

Journal of Extracellular Vesicles
Yinuo LinHong Yu

Abstract

Exosomes play a critical role in intercellular communication since they contain signalling molecules and genetic materials. During tumorigenesis, tumour-derived exosomes have been demonstrated to promote tumour angiogenesis and metastasis. However, how the exosomes facilitate tumour metastasis is not clear. Here we explored the effect of HeLa cell-derived exosomes (ExoHeLa) on endothelial tight junctions (TJ) and the related mechanisms. After human umbilical vein endothelial cells (HUVEC) were treated with ExoHeLa, TJ proteins zonula occludens-1 (ZO-1) and Claudin-5 in HUVEC were significantly reduced as compared with that treated with exosomes from human cervical epithelial cells, while mRNA levels of ZO-1 and Claudin-5 remained unchanged. Consequently, permeability of endothelial monolayer was increased after the treatment with ExoHeLa. Injection of ExoHeLa into mice also increased vascular permeability and tumour metastasis in vivo. Neither knocking down of Dicer nor use of inhibitors of microRNAs targeting at mRNAs of ZO-1 and Claudin-5 could block the inhibitory effect of ExoHeLa on ZO-1 and Claudin-5. The expression of genes involved in endoplasmic reticulum (ER) stress was significantly increased in HUVECs after treated ...Continue Reading

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Citations

Jul 6, 2020·International Journal of Cancer. Journal International Du Cancer·Ursula AltanerovaCestmir Altaner
Sep 19, 2020·International Journal of Molecular Sciences·Claudia CavallariMaria Felice Brizzi
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Aug 7, 2021·Advanced Drug Delivery Reviews·Peiwen FuZhimin Tao

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Datasets Mentioned

BETA
GSE128803
GM130

Methods Mentioned

BETA
transmission electron microscopy
protein assay
Assay
PCR
RNA-Seq
electrophoresis
Chip
transfection
reversed-phase chromatography
Fluorescence

Software Mentioned

image J
Miranda
TargetScan
RNAhybrid
SPSS

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