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Tumor-Educated Platelets and Angiogenesis in Glioblastoma: Another Brick in the Wall for Novel Prognostic and Targetable Biomarkers, Changing the Vision from a Localized Tumor to a Systemic Pathology

Circulating platelets (PLTs) are able to affect glioblastoma (GBM) microenvironment by supplying oncopromoter and pro-angiogenic factors. Among these mediators, sphingosine-1-phophate (S1P) has emerged as a potent bioactive lipid enhancing cell proliferation and survival. Here, we investigated the e...

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Autores principales: Campanella, Rolando, Guarnaccia, Laura, Cordiglieri, Chiara, Trombetta, Elena, Caroli, Manuela, Carrabba, Giorgio, La Verde, Nicla, Rampini, Paolo, Gaudino, Chiara, Costa, Antonella, Luzzi, Sabino, Mantovani, Giovanna, Locatelli, Marco, Riboni, Laura, Navone, Stefania Elena, Marfia, Giovanni
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7072723/
https://www.ncbi.nlm.nih.gov/pubmed/31991805
http://dx.doi.org/10.3390/cells9020294
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author Campanella, Rolando
Guarnaccia, Laura
Cordiglieri, Chiara
Trombetta, Elena
Caroli, Manuela
Carrabba, Giorgio
La Verde, Nicla
Rampini, Paolo
Gaudino, Chiara
Costa, Antonella
Luzzi, Sabino
Mantovani, Giovanna
Locatelli, Marco
Riboni, Laura
Navone, Stefania Elena
Marfia, Giovanni
author_facet Campanella, Rolando
Guarnaccia, Laura
Cordiglieri, Chiara
Trombetta, Elena
Caroli, Manuela
Carrabba, Giorgio
La Verde, Nicla
Rampini, Paolo
Gaudino, Chiara
Costa, Antonella
Luzzi, Sabino
Mantovani, Giovanna
Locatelli, Marco
Riboni, Laura
Navone, Stefania Elena
Marfia, Giovanni
author_sort Campanella, Rolando
collection PubMed
description Circulating platelets (PLTs) are able to affect glioblastoma (GBM) microenvironment by supplying oncopromoter and pro-angiogenic factors. Among these mediators, sphingosine-1-phophate (S1P) has emerged as a potent bioactive lipid enhancing cell proliferation and survival. Here, we investigated the effect of “tumor education”, characterizing PLTs from GBM patients in terms of activation state, protein content, and pro-angiogenic potential. PLTs from healthy donors (HD-PLTs) and GBM patients (GBM-PLTs) were collected, activated, and analyzed by flow cytometry, immunofluorescence, and Western blotting. To assess the pro-angiogenic contribution of GBM-PLTs, a functional cord formation assay was performed on GBM endothelial cells (GECs) with PLT-releasate. GBM-PLTs expressed higher positivity for P-selectin compared to HD-PLTs, both in basal conditions and after stimulation with adenosine triphosphate (ADP) and thrombin receptor activating peptide (TRAP). PLTs showed higher expression of VEGFR-1, VEGFR-2, VWF, S1P, S1PR1, SphK1, and SPNS. Interestingly, increased concentrations of VEGF and its receptors VEGFR1 and VEGFR2, VWF, and S1P were found in GBM-PLT-releasate with respect to HD-PLTs. Finally, GBM-PLT-releasate showed a pro-angiogenic effect on GECs, increasing the vascular network’s complexity. Overall, our results demonstrated the contribution of PLTs to GBM angiogenesis and aggressiveness, advancing the potential of an anti-PLT therapy and the usefulness of PLT cargo as predictive and monitoring biomarkers.
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spelling pubmed-70727232020-03-19 Tumor-Educated Platelets and Angiogenesis in Glioblastoma: Another Brick in the Wall for Novel Prognostic and Targetable Biomarkers, Changing the Vision from a Localized Tumor to a Systemic Pathology Campanella, Rolando Guarnaccia, Laura Cordiglieri, Chiara Trombetta, Elena Caroli, Manuela Carrabba, Giorgio La Verde, Nicla Rampini, Paolo Gaudino, Chiara Costa, Antonella Luzzi, Sabino Mantovani, Giovanna Locatelli, Marco Riboni, Laura Navone, Stefania Elena Marfia, Giovanni Cells Communication Circulating platelets (PLTs) are able to affect glioblastoma (GBM) microenvironment by supplying oncopromoter and pro-angiogenic factors. Among these mediators, sphingosine-1-phophate (S1P) has emerged as a potent bioactive lipid enhancing cell proliferation and survival. Here, we investigated the effect of “tumor education”, characterizing PLTs from GBM patients in terms of activation state, protein content, and pro-angiogenic potential. PLTs from healthy donors (HD-PLTs) and GBM patients (GBM-PLTs) were collected, activated, and analyzed by flow cytometry, immunofluorescence, and Western blotting. To assess the pro-angiogenic contribution of GBM-PLTs, a functional cord formation assay was performed on GBM endothelial cells (GECs) with PLT-releasate. GBM-PLTs expressed higher positivity for P-selectin compared to HD-PLTs, both in basal conditions and after stimulation with adenosine triphosphate (ADP) and thrombin receptor activating peptide (TRAP). PLTs showed higher expression of VEGFR-1, VEGFR-2, VWF, S1P, S1PR1, SphK1, and SPNS. Interestingly, increased concentrations of VEGF and its receptors VEGFR1 and VEGFR2, VWF, and S1P were found in GBM-PLT-releasate with respect to HD-PLTs. Finally, GBM-PLT-releasate showed a pro-angiogenic effect on GECs, increasing the vascular network’s complexity. Overall, our results demonstrated the contribution of PLTs to GBM angiogenesis and aggressiveness, advancing the potential of an anti-PLT therapy and the usefulness of PLT cargo as predictive and monitoring biomarkers. MDPI 2020-01-25 /pmc/articles/PMC7072723/ /pubmed/31991805 http://dx.doi.org/10.3390/cells9020294 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Communication
Campanella, Rolando
Guarnaccia, Laura
Cordiglieri, Chiara
Trombetta, Elena
Caroli, Manuela
Carrabba, Giorgio
La Verde, Nicla
Rampini, Paolo
Gaudino, Chiara
Costa, Antonella
Luzzi, Sabino
Mantovani, Giovanna
Locatelli, Marco
Riboni, Laura
Navone, Stefania Elena
Marfia, Giovanni
Tumor-Educated Platelets and Angiogenesis in Glioblastoma: Another Brick in the Wall for Novel Prognostic and Targetable Biomarkers, Changing the Vision from a Localized Tumor to a Systemic Pathology
title Tumor-Educated Platelets and Angiogenesis in Glioblastoma: Another Brick in the Wall for Novel Prognostic and Targetable Biomarkers, Changing the Vision from a Localized Tumor to a Systemic Pathology
title_full Tumor-Educated Platelets and Angiogenesis in Glioblastoma: Another Brick in the Wall for Novel Prognostic and Targetable Biomarkers, Changing the Vision from a Localized Tumor to a Systemic Pathology
title_fullStr Tumor-Educated Platelets and Angiogenesis in Glioblastoma: Another Brick in the Wall for Novel Prognostic and Targetable Biomarkers, Changing the Vision from a Localized Tumor to a Systemic Pathology
title_full_unstemmed Tumor-Educated Platelets and Angiogenesis in Glioblastoma: Another Brick in the Wall for Novel Prognostic and Targetable Biomarkers, Changing the Vision from a Localized Tumor to a Systemic Pathology
title_short Tumor-Educated Platelets and Angiogenesis in Glioblastoma: Another Brick in the Wall for Novel Prognostic and Targetable Biomarkers, Changing the Vision from a Localized Tumor to a Systemic Pathology
title_sort tumor-educated platelets and angiogenesis in glioblastoma: another brick in the wall for novel prognostic and targetable biomarkers, changing the vision from a localized tumor to a systemic pathology
topic Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7072723/
https://www.ncbi.nlm.nih.gov/pubmed/31991805
http://dx.doi.org/10.3390/cells9020294
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