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Monocytes as Endothelial Progenitor Cells (EPCs), Another Brick in the Wall to Disentangle Tumor Angiogenesis
Open AccessCommunication

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

1
Laboratory of Experimental Neurosurgery and Cell Therapy, Neurosurgery Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy
2
Department of Clinical Sciences and Community Health, University of Milan, 20122 Milan, Italy
3
Imaging Facility, National Institute for Molecular Genetics (INGM), 20122 Milan, Italy
4
Flow Cytometry Service, Clinical Laboratory, Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy
5
Oncology Unit, ASST Sacco Hospital, 20157 Milan, Italy
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Department of Neuroradiology, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, University of Milan, 20122 Milan, Italy
7
Neurosurgery Unit, Department of Clinical-Surgical, Diagnostic and Pediatric Sciences, University of Pavia, 27100 Pavia, Italy
8
Neurosurgery Unit, Department of Surgical Sciences, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy
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Endocrinology Unit, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, 20122 Milan, Italy
10
Department of Medical-Surgical Physiopathology and Transplantation, University of Milan, 20122 Milan, Italy
11
Department of Medical Biotechnology and Translational Medicine, LITA-Segrate, University of Milan, 20090 Milan, Italy
*
Author to whom correspondence should be addressed.
These authors contribute equally.
These authors contribute equally.
Cells 2020, 9(2), 294; https://doi.org/10.3390/cells9020294 (registering DOI)
Received: 6 December 2019 / Revised: 13 January 2020 / Accepted: 22 January 2020 / Published: 25 January 2020
(This article belongs to the Special Issue Angiogenesis in Cancer)
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. View Full-Text
Keywords: glioblastoma; platelets; sphingosine-1-phosphate; angiogenesis glioblastoma; platelets; sphingosine-1-phosphate; angiogenesis
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Campanella, R.; Guarnaccia, L.; Cordiglieri, C.; Trombetta, E.; Caroli, M.; Carrabba, G.; La Verde, N.; Rampini, P.; Gaudino, C.; Costa, A.; Luzzi, S.; Mantovani, G.; Locatelli, M.; Riboni, L.; Navone, S.E.; Marfia, G. 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. Cells 2020, 9, 294.

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