Abstract
Glioblastoma (GBM), a high-grade glioma (WHO grade IV), is the most aggressive form of brain cancer. Available treatment options for GBM involve a combination of surgery, radiation and chemotherapy but result in a poor survival outcome. GBM is a high-vascularized tumor and antiangiogenic drugs are widely used in GBM therapy as adjuvants to control abnormal vasculature. Vasculogenic mimicry occurs in GBM as an alternative vascularization mechanism, providing a means whereby GBM can escape anti-angiogenic therapies. Here, using an in vitro tube formation assay on Matrigel®, we evaluated the ability of different histone deacetylase inhibitors (HDACis) to interfere with vasculogenic mimicry. We found that vorinostat (SAHA) and MC1568 inhibit tube formation by rat glioma C6 cells. Moreover, at sublethal doses for GBM cells, SAHA, trichostatin A (TSA), entinostat (MS275), and MC1568 significantly decrease tube formation by U87MG and by patient-derived human GBM cancer stem cells (CSCs). The reduced migration and invasion of HDACis-treated U87 cells, at least in part, may account for the inhibition of tube formation. In conclusion, our results indicate that HDACis are promising candidates for blocking vascular mimicry in GBM.
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Details
Published
May 29, 2019
Vol/Issue
11(6)
Pages
747
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Authors
Funding
Regione Campania Award: FASE2-IDEAL
PRIN Award: 20152TE5PK
AIRC Award: 17217
POR Award: SATIN
FP7-BLUEPRINT Award: 282510
Lotta alle patologie concologiche Award: iCURE
progetti retrospettivi progetto MERCURIO Award: FESR
Università della Campania Luigi Vanvitelli Award: progetto VALERE,
BioUp Sagl Award: BioUp Sagl
Cite This Article
Olga Pastorino, Maria Teresa Gentile, Alessandro Mancini, et al. (2019). Histone Deacetylase Inhibitors Impair Vasculogenic Mimicry from Glioblastoma Cells. Cancers, 11(6), 747. https://doi.org/10.3390/cancers11060747