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.

Campanella, R., Guarnaccia, L., Cordiglieri, C., Trombetta, E., Caroli, M., Carrabba, G., et al. (2020). 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, 9(2), 1-15 [10.3390/cells9020294].

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

Carrabba, Giorgio;
2020

Abstract

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.
Articolo in rivista - Articolo scientifico
angiogenesis; glioblastoma; platelets; sphingosine-1-phosphate;
English
1
15
15
Campanella, R., Guarnaccia, L., Cordiglieri, C., Trombetta, E., Caroli, M., Carrabba, G., et al. (2020). 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, 9(2), 1-15 [10.3390/cells9020294].
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; Marfia, G
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/355763
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