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Proteomic and functional profiling of platelet-derived extracellular vesicles released under physiological or tumor-associated conditions

During hemostasis, thrombosis, and inflammation, activated blood platelets release extracellular vesicles (PEVs) that represent biological mediators of physiological and pathological processes. We have recently demonstrated that the activation of platelets by breast cancer cells is accompanied by a...

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Autores principales: Vismara, Mauro, Manfredi, Marcello, Zarà, Marta, Trivigno, Silvia Maria Grazia, Galgano, Luca, Barbieri, Silvia Stella, Canobbio, Ilaria, Torti, Mauro, Guidetti, Gianni Francesco
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9701234/
https://www.ncbi.nlm.nih.gov/pubmed/36435831
http://dx.doi.org/10.1038/s41420-022-01263-3
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author Vismara, Mauro
Manfredi, Marcello
Zarà, Marta
Trivigno, Silvia Maria Grazia
Galgano, Luca
Barbieri, Silvia Stella
Canobbio, Ilaria
Torti, Mauro
Guidetti, Gianni Francesco
author_facet Vismara, Mauro
Manfredi, Marcello
Zarà, Marta
Trivigno, Silvia Maria Grazia
Galgano, Luca
Barbieri, Silvia Stella
Canobbio, Ilaria
Torti, Mauro
Guidetti, Gianni Francesco
author_sort Vismara, Mauro
collection PubMed
description During hemostasis, thrombosis, and inflammation, activated blood platelets release extracellular vesicles (PEVs) that represent biological mediators of physiological and pathological processes. We have recently demonstrated that the activation of platelets by breast cancer cells is accompanied by a massive release of PEVs, evidence that matches with the observation that breast cancer patients display increased levels of circulating PEVs. A core concept in PEVs biology is that their nature, composition and biological function are strongly influenced by the conditions that induced their release. In this study we have performed a comparative characterization of PEVs released by platelets upon activation with thrombin, a potent thrombotic stimulus, and upon exposure to the breast cancer cell line MDA-MB-231. By nanoparticle tracking analysis and tandem mass spectrometry we have characterized the two populations of PEVs, showing that the thrombotic and tumoral stimuli produced vesicles that largely differ in protein composition. The bioinformatic analysis of the proteomic data led to the identification of signaling pathways that can be differently affected by the two PEVs population in target cells. Specifically, we have demonstrated that both thrombin- and cancer-cell-induced PEVs reduce the migration and potentiate Ca(2+)-induced apoptosis of Jurkat cells, but only thrombin-derived PEVs also potentiate cell necrosis. Our results demonstrate that stimulation of platelets by thrombotic or tumoral stimuli induces the release of PEVs with different protein composition that, in turn, may elicit selective biological responses in target cells.
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spelling pubmed-97012342022-11-28 Proteomic and functional profiling of platelet-derived extracellular vesicles released under physiological or tumor-associated conditions Vismara, Mauro Manfredi, Marcello Zarà, Marta Trivigno, Silvia Maria Grazia Galgano, Luca Barbieri, Silvia Stella Canobbio, Ilaria Torti, Mauro Guidetti, Gianni Francesco Cell Death Discov Article During hemostasis, thrombosis, and inflammation, activated blood platelets release extracellular vesicles (PEVs) that represent biological mediators of physiological and pathological processes. We have recently demonstrated that the activation of platelets by breast cancer cells is accompanied by a massive release of PEVs, evidence that matches with the observation that breast cancer patients display increased levels of circulating PEVs. A core concept in PEVs biology is that their nature, composition and biological function are strongly influenced by the conditions that induced their release. In this study we have performed a comparative characterization of PEVs released by platelets upon activation with thrombin, a potent thrombotic stimulus, and upon exposure to the breast cancer cell line MDA-MB-231. By nanoparticle tracking analysis and tandem mass spectrometry we have characterized the two populations of PEVs, showing that the thrombotic and tumoral stimuli produced vesicles that largely differ in protein composition. The bioinformatic analysis of the proteomic data led to the identification of signaling pathways that can be differently affected by the two PEVs population in target cells. Specifically, we have demonstrated that both thrombin- and cancer-cell-induced PEVs reduce the migration and potentiate Ca(2+)-induced apoptosis of Jurkat cells, but only thrombin-derived PEVs also potentiate cell necrosis. Our results demonstrate that stimulation of platelets by thrombotic or tumoral stimuli induces the release of PEVs with different protein composition that, in turn, may elicit selective biological responses in target cells. Nature Publishing Group UK 2022-11-26 /pmc/articles/PMC9701234/ /pubmed/36435831 http://dx.doi.org/10.1038/s41420-022-01263-3 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Vismara, Mauro
Manfredi, Marcello
Zarà, Marta
Trivigno, Silvia Maria Grazia
Galgano, Luca
Barbieri, Silvia Stella
Canobbio, Ilaria
Torti, Mauro
Guidetti, Gianni Francesco
Proteomic and functional profiling of platelet-derived extracellular vesicles released under physiological or tumor-associated conditions
title Proteomic and functional profiling of platelet-derived extracellular vesicles released under physiological or tumor-associated conditions
title_full Proteomic and functional profiling of platelet-derived extracellular vesicles released under physiological or tumor-associated conditions
title_fullStr Proteomic and functional profiling of platelet-derived extracellular vesicles released under physiological or tumor-associated conditions
title_full_unstemmed Proteomic and functional profiling of platelet-derived extracellular vesicles released under physiological or tumor-associated conditions
title_short Proteomic and functional profiling of platelet-derived extracellular vesicles released under physiological or tumor-associated conditions
title_sort proteomic and functional profiling of platelet-derived extracellular vesicles released under physiological or tumor-associated conditions
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9701234/
https://www.ncbi.nlm.nih.gov/pubmed/36435831
http://dx.doi.org/10.1038/s41420-022-01263-3
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