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| Cholangiocarcinoma derived exosomes break down vascular integrity and cause metastasis by triggering endoplasmic reticulum stress in vascular endothelial cells |
| LI Zhengzheng1, SUN Hongwei2, ZHANG Nan1, SU Huafang3 |
| 1.Department of Neurology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325015, China; 2.Department of Hepatobiliary Surgery, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325015, China; 3.Department of Chemotherapy, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325015, China |
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| Cite this article: |
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LI Zhengzheng,SUN Hongwei,ZHANG Nan, et al. Cholangiocarcinoma derived exosomes break down vascular integrity and cause metastasis by triggering endoplasmic reticulum stress in vascular endothelial cells[J]. JOURNAL OF WEZHOU MEDICAL UNIVERSITY, 2019, 49(4): 235-242.
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Abstract Objective: To explore the effects of cholangiocarcinoma exosomes on the endothelial tight junction and the possible underlying mechanism. Methods: Exosomes were isolated from the supernatant of cholangiocarcinoma cell line CCLP and human intrahepatic bile duct epithelial cells (HIBEC) by ultracentrifugation according to the well-established protocol and were administrated to human umbilical vein endothelial cells (HUVEC), PBS was chosen as control. Endothelial monolayer permeability was assessed in vitro and tight junction proteins (TJPs) were evaluated by Western blot and immunofluorescence. BALB/c null mice were divided as three groups (PBS, exoCCLP and exoHIBEC), which were administrated with PBS, CCLP exosomes or HIBEC exosomes via tail vein respectively for indicated durations. FITC-Dextran or CCLP were then injected intravenously and leakage of FITC-Dextran in lung and liver, or pulmonary metastases were assessed. The endoplasmic reticulum stress related genes and proteins were analyzed by real-time PCR and Western blot. Endothelial PERK, ATF6 or IRE1α were partially knocked down by siRNA before HUVECs were treated with CCLP exosomes, and TJPs were evaluated afterwards. Results: CCLP exosomes downregulated the expression of TJPs in HUVECs, and increased the permeability of endothelial monolayer in vitro. In vivo experiments indicated that compared to
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Received: 07 November 2018
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