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.
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 / R. Campanella, L. Guarnaccia, C. Cordiglieri, E. Trombetta, M. Caroli, G. Carrabba, N. La Verde, P. Rampini, C. Gaudino, A. Costa, S. Luzzi, G. Mantovani, M. Locatelli, L. Riboni, S.E. Navone, G. Marfia. - In: CELLS. - ISSN 2073-4409. - 9:2(2020 Jan 25), pp. 294.1-294.15.
|Titolo:||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|
|Parole Chiave:||angiogenesis; glioblastoma; platelets; sphingosine-1-phosphate|
|Settore Scientifico Disciplinare:||Settore BIO/10 - Biochimica|
Settore MED/27 - Neurochirurgia
|Data di pubblicazione:||25-gen-2020|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.3390/cells9020294|
|Appare nelle tipologie:||01 - Articolo su periodico|