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Cancer cell–derived microparticles bearing P-selectin glycoprotein ligand 1 accelerate thrombus formation in vivo

Recent publications have demonstrated the presence of tissue factor (TF)–bearing microparticles (MPs) in the blood of patients suffering from cancer. However, whether these MPs are involved in thrombosis remains unknown. We show that pancreatic and lung cancer cells produce MPs that express active T...

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Autores principales: Thomas, Grace M., Panicot-Dubois, Laurence, Lacroix, Romaric, Dignat-George, Françoise, Lombardo, Dominique, Dubois, Christophe
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2737159/
https://www.ncbi.nlm.nih.gov/pubmed/19667060
http://dx.doi.org/10.1084/jem.20082297
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author Thomas, Grace M.
Panicot-Dubois, Laurence
Lacroix, Romaric
Dignat-George, Françoise
Lombardo, Dominique
Dubois, Christophe
author_facet Thomas, Grace M.
Panicot-Dubois, Laurence
Lacroix, Romaric
Dignat-George, Françoise
Lombardo, Dominique
Dubois, Christophe
author_sort Thomas, Grace M.
collection PubMed
description Recent publications have demonstrated the presence of tissue factor (TF)–bearing microparticles (MPs) in the blood of patients suffering from cancer. However, whether these MPs are involved in thrombosis remains unknown. We show that pancreatic and lung cancer cells produce MPs that express active TF and P-selectin glycoprotein ligand 1 (PSGL-1). Cancer cell–derived MPs aggregate platelets via a TF-dependent pathway. In vivo, cancer cell–derived MPs, but not their parent cells, infused into a living mouse accumulate at the site of injury and reduce tail bleeding time and the time to occlusion of venules and arterioles. This thrombotic state is also observed in mice developing tumors. In such mice, the amount of circulating platelet-, endothelial cell–, and cancer cell–derived MPs is increased. Endogenous cancer cell–derived MPs shed from the growing tumor are able to accumulate at the site of injury. Infusion of a blocking P-selectin antibody abolishes the thrombotic state observed after injection of MPs or in mice developing a tumor. Collectively, our results indicate that cancer cell–derived MPs bearing PSGL-1 and TF play a key role in thrombus formation in vivo. Targeting these MPs could be of clinical interest in the prevention of thrombosis and to limit formation of metastasis in cancer patients.
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spelling pubmed-27371592010-02-28 Cancer cell–derived microparticles bearing P-selectin glycoprotein ligand 1 accelerate thrombus formation in vivo Thomas, Grace M. Panicot-Dubois, Laurence Lacroix, Romaric Dignat-George, Françoise Lombardo, Dominique Dubois, Christophe J Exp Med Article Recent publications have demonstrated the presence of tissue factor (TF)–bearing microparticles (MPs) in the blood of patients suffering from cancer. However, whether these MPs are involved in thrombosis remains unknown. We show that pancreatic and lung cancer cells produce MPs that express active TF and P-selectin glycoprotein ligand 1 (PSGL-1). Cancer cell–derived MPs aggregate platelets via a TF-dependent pathway. In vivo, cancer cell–derived MPs, but not their parent cells, infused into a living mouse accumulate at the site of injury and reduce tail bleeding time and the time to occlusion of venules and arterioles. This thrombotic state is also observed in mice developing tumors. In such mice, the amount of circulating platelet-, endothelial cell–, and cancer cell–derived MPs is increased. Endogenous cancer cell–derived MPs shed from the growing tumor are able to accumulate at the site of injury. Infusion of a blocking P-selectin antibody abolishes the thrombotic state observed after injection of MPs or in mice developing a tumor. Collectively, our results indicate that cancer cell–derived MPs bearing PSGL-1 and TF play a key role in thrombus formation in vivo. Targeting these MPs could be of clinical interest in the prevention of thrombosis and to limit formation of metastasis in cancer patients. The Rockefeller University Press 2009-08-31 /pmc/articles/PMC2737159/ /pubmed/19667060 http://dx.doi.org/10.1084/jem.20082297 Text en © 2009 Thomas et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jem.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Article
Thomas, Grace M.
Panicot-Dubois, Laurence
Lacroix, Romaric
Dignat-George, Françoise
Lombardo, Dominique
Dubois, Christophe
Cancer cell–derived microparticles bearing P-selectin glycoprotein ligand 1 accelerate thrombus formation in vivo
title Cancer cell–derived microparticles bearing P-selectin glycoprotein ligand 1 accelerate thrombus formation in vivo
title_full Cancer cell–derived microparticles bearing P-selectin glycoprotein ligand 1 accelerate thrombus formation in vivo
title_fullStr Cancer cell–derived microparticles bearing P-selectin glycoprotein ligand 1 accelerate thrombus formation in vivo
title_full_unstemmed Cancer cell–derived microparticles bearing P-selectin glycoprotein ligand 1 accelerate thrombus formation in vivo
title_short Cancer cell–derived microparticles bearing P-selectin glycoprotein ligand 1 accelerate thrombus formation in vivo
title_sort cancer cell–derived microparticles bearing p-selectin glycoprotein ligand 1 accelerate thrombus formation in vivo
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2737159/
https://www.ncbi.nlm.nih.gov/pubmed/19667060
http://dx.doi.org/10.1084/jem.20082297
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