Histone deacetylase inhibitors impair vasculogenic mimicry from glioblastoma cells

Luca Colucci-D’amato, Olga Pastorino, Maria Teresa Gentile, Alessandro Mancini, Nunzio Del Gaudio, Antonella Di Costanzo, Adriana Bajetto, Paola Franco, Lucia Altucci, Tullio Florio, Maria Patrizia Stoppelli

Research output: Contribution to journalArticle

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.

Original languageEnglish
Article number747
JournalCancers
Volume11
Issue number6
DOIs
Publication statusPublished - Jun 1 2019

Keywords

  • Angiogenesis
  • Cancer stem cells
  • Cell invasion
  • Cell migration
  • Glioblastoma
  • HDAC
  • Vasculogenic mimicry

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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