Isolated tumour microparticles induce endothelial microparticle release in vitro

Faulkner, Lucy G.; Alqarni, Saeed; Maraveyas, Anthony; Madden, Leigh A.

Abstract

© 2019 Wolters Kluwer Health, Inc. All rights reserved. Cancer induces a hypercoagulable state, resulting in an increased risk of venous thromboembolism. One of the mechanisms driving this is tissue factor (TF) production by the tumour, released in small lipid bound microparticles. We have previously demonstrated that tumour cell line media-induced procoagulant changes in HUVEC. The aim of this study was to investigate the effect of tumour microparticles and recombinant human TF (rhTF) on the endothelium. Procoagulant microparticles from the PANC-1 cell line were harvested by ultrafiltration. HUVEC were then incubated with these procoagulant microparticles or rhTF. Flow cytometry was used to investigate the effect of endothelial cell surface protein expression and microparticle release. Microparticles but not soluble TF was responsible for the procoagulant activity of cell-free tumour media. We also demonstrated an increase in endothelial microparticle release with exposure to tumour microparticles, with a positive linear relationship observed (R2 = 0.6630 P ≤ 0.0001). rhTF did not induce any of the changes observed with microparticles. Here we demonstrate that procoagulant activity of tumour cell line media is dependent on microparticles, and that exposure of endothelial cells to these microparticles results in an increase in microparticle release from HUVEC. This suggests a mechanism of transfer of procoagulant potential from the cancer to the remote endothelium.

Citation

Faulkner, L. G., Alqarni, S., Maraveyas, A., & Madden, L. A. (2020). Isolated tumour microparticles induce endothelial microparticle release in vitro. Blood Coagulation and Fibrinolysis, 31(1), 35-42. https://doi.org/10.1097/MBC.0000000000000876

• Journal Article Type: Article
• Acceptance Date: Nov 5, 2019
• Online Publication Date: Nov 26, 2019
• Publication Date: Jan 1, 2020
• Deposit Date: Nov 25, 2019
• Publicly Available Date: Nov 27, 2020
• Journal: Blood Coagulation and Fibrinolysis
• Print ISSN: 0957-5235
• Publisher: Lippincott, Williams & Wilkins
• Peer Reviewed: Peer Reviewed
• Volume: 31
• Issue: 1
• Pages: 35-42
• DOI: https://doi.org/10.1097/MBC.0000000000000876
• Keywords: Microparticles; Microvesicles; Venous thromboembolism; Endothelium; Cancer.
• Public URL: https://hull-repository.worktribe.com/output/3155923
• Contract Date: Nov 26, 2019