Platelets from glioblastoma patients promote angiogenesis of tumor endothelial cells and exhibit increased VEGF content and release

Glioblastoma multiforme (GBM) is the most common and fatal intracranial cancer in humans and exhibits intense and aberrant angiogenesis that sustains its malignancy and involves several angiogenic signals. Among them, vascular endothelial growth factor (VEGF) plays a key role and is overexpressed in...

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Main Authors: Clara Di Vito, Stefania Elena Navone, Giovanni Marfia, Loubna Abdel Hadi, Maria Elisa Mancuso, Alessandro Pecci, Francesco Maria Crisà, Valeria Berno, Paolo Rampini, Rolando Campanella, Laura Riboni
Format: Article
Language:English
Published: Taylor & Francis Group 2017-08-01
Series:Platelets
Subjects:
Online Access:http://dx.doi.org/10.1080/09537104.2016.1247208
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author Clara Di Vito
Stefania Elena Navone
Giovanni Marfia
Loubna Abdel Hadi
Maria Elisa Mancuso
Alessandro Pecci
Francesco Maria Crisà
Valeria Berno
Paolo Rampini
Rolando Campanella
Laura Riboni
author_facet Clara Di Vito
Stefania Elena Navone
Giovanni Marfia
Loubna Abdel Hadi
Maria Elisa Mancuso
Alessandro Pecci
Francesco Maria Crisà
Valeria Berno
Paolo Rampini
Rolando Campanella
Laura Riboni
author_sort Clara Di Vito
collection DOAJ
description Glioblastoma multiforme (GBM) is the most common and fatal intracranial cancer in humans and exhibits intense and aberrant angiogenesis that sustains its malignancy and involves several angiogenic signals. Among them, vascular endothelial growth factor (VEGF) plays a key role and is overexpressed in GBM. Different cells appear to act as triggers of the aberrant angiogenesis, and, among them, platelets act as key participants. In order to provide further insights into the platelet features and angiogenic role in GBM, this study investigated the effects of platelet releasate on GBM-derived endothelial cells (GECs) and the levels of VEGF and endostatin, as pro- and anti-angiogenic components of platelet releasate from GBM patients. We demonstrate for the first time that: 1) platelet releasate exerts powerful pro-angiogenic effect on GECs, suggesting it might exert a role in the aberrant angiogenesis of GBM; 2) ADP and thrombin stimulation leads to significantly higher level of VEGF, but not of endostatin, in the releasate of platelets from GBM patients than those from healthy subjects; and 3) the intraplatelet concentrations of VEGF were significantly elevated in GBM patients as compared to controls. Moreover, we found a direct correlation between platelet-released VEGF and overall survival in our patient cohort. Although preliminary, these findings prompt further investigations to clarify the biologic relevance of platelet VEGF in GBM and prospective studies for screening GBM patients for anti-VEGF therapy and/or to optimize this treatment.
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spelling doaj.art-a37d6a76cd2a4fb8a7ec76a45a912e722023-09-15T10:31:56ZengTaylor & Francis GroupPlatelets0953-71041369-16352017-08-0128658559410.1080/09537104.2016.12472081247208Platelets from glioblastoma patients promote angiogenesis of tumor endothelial cells and exhibit increased VEGF content and releaseClara Di Vito0Stefania Elena Navone1Giovanni Marfia2Loubna Abdel Hadi3Maria Elisa Mancuso4Alessandro Pecci5Francesco Maria Crisà6Valeria Berno7Paolo Rampini8Rolando Campanella9Laura Riboni10LITA-Segrate, University of MilanUniversity of MilanUniversity of MilanLITA-Segrate, University of MilanAngelo Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Cà Granda, Ospedale Maggiore PoliclinicoIRCCS Policlinico San Matteo Foundation, University of PaviaUniversity of MilanFondazione Istituto Nazionale di Genetica Molecolare “Romeo ed Enrica Invernizzi”University of MilanUniversity of MilanLITA-Segrate, University of MilanGlioblastoma multiforme (GBM) is the most common and fatal intracranial cancer in humans and exhibits intense and aberrant angiogenesis that sustains its malignancy and involves several angiogenic signals. Among them, vascular endothelial growth factor (VEGF) plays a key role and is overexpressed in GBM. Different cells appear to act as triggers of the aberrant angiogenesis, and, among them, platelets act as key participants. In order to provide further insights into the platelet features and angiogenic role in GBM, this study investigated the effects of platelet releasate on GBM-derived endothelial cells (GECs) and the levels of VEGF and endostatin, as pro- and anti-angiogenic components of platelet releasate from GBM patients. We demonstrate for the first time that: 1) platelet releasate exerts powerful pro-angiogenic effect on GECs, suggesting it might exert a role in the aberrant angiogenesis of GBM; 2) ADP and thrombin stimulation leads to significantly higher level of VEGF, but not of endostatin, in the releasate of platelets from GBM patients than those from healthy subjects; and 3) the intraplatelet concentrations of VEGF were significantly elevated in GBM patients as compared to controls. Moreover, we found a direct correlation between platelet-released VEGF and overall survival in our patient cohort. Although preliminary, these findings prompt further investigations to clarify the biologic relevance of platelet VEGF in GBM and prospective studies for screening GBM patients for anti-VEGF therapy and/or to optimize this treatment.http://dx.doi.org/10.1080/09537104.2016.1247208glioblastomaplateletstumor endothelial cellsvegf
spellingShingle Clara Di Vito
Stefania Elena Navone
Giovanni Marfia
Loubna Abdel Hadi
Maria Elisa Mancuso
Alessandro Pecci
Francesco Maria Crisà
Valeria Berno
Paolo Rampini
Rolando Campanella
Laura Riboni
Platelets from glioblastoma patients promote angiogenesis of tumor endothelial cells and exhibit increased VEGF content and release
Platelets
glioblastoma
platelets
tumor endothelial cells
vegf
title Platelets from glioblastoma patients promote angiogenesis of tumor endothelial cells and exhibit increased VEGF content and release
title_full Platelets from glioblastoma patients promote angiogenesis of tumor endothelial cells and exhibit increased VEGF content and release
title_fullStr Platelets from glioblastoma patients promote angiogenesis of tumor endothelial cells and exhibit increased VEGF content and release
title_full_unstemmed Platelets from glioblastoma patients promote angiogenesis of tumor endothelial cells and exhibit increased VEGF content and release
title_short Platelets from glioblastoma patients promote angiogenesis of tumor endothelial cells and exhibit increased VEGF content and release
title_sort platelets from glioblastoma patients promote angiogenesis of tumor endothelial cells and exhibit increased vegf content and release
topic glioblastoma
platelets
tumor endothelial cells
vegf
url http://dx.doi.org/10.1080/09537104.2016.1247208
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