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

Fingerprint

Histone Deacetylase Inhibitors
Glioblastoma
Glioma
trichostatin A
Neoplastic Stem Cells
Brain Neoplasms
Blood Vessels
Therapeutics
Radiation
Drug Therapy
Survival

Keywords

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

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Colucci-D’amato, L., Pastorino, O., Teresa Gentile, M., Mancini, A., Del Gaudio, N., Di Costanzo, A., ... Patrizia Stoppelli, M. (2019). Histone deacetylase inhibitors impair vasculogenic mimicry from glioblastoma cells. Cancers, 11(6), [747]. https://doi.org/10.3390/cancers11060747

Histone deacetylase inhibitors impair vasculogenic mimicry from glioblastoma cells. / Colucci-D’amato, Luca; Pastorino, Olga; Teresa Gentile, Maria; Mancini, Alessandro; Del Gaudio, Nunzio; Di Costanzo, Antonella; Bajetto, Adriana; Franco, Paola; Altucci, Lucia; Florio, Tullio; Patrizia Stoppelli, Maria.

In: Cancers, Vol. 11, No. 6, 747, 01.06.2019.

Research output: Contribution to journalArticle

Colucci-D’amato, L, Pastorino, O, Teresa Gentile, M, Mancini, A, Del Gaudio, N, Di Costanzo, A, Bajetto, A, Franco, P, Altucci, L, Florio, T & Patrizia Stoppelli, M 2019, 'Histone deacetylase inhibitors impair vasculogenic mimicry from glioblastoma cells', Cancers, vol. 11, no. 6, 747. https://doi.org/10.3390/cancers11060747
Colucci-D’amato L, Pastorino O, Teresa Gentile M, Mancini A, Del Gaudio N, Di Costanzo A et al. Histone deacetylase inhibitors impair vasculogenic mimicry from glioblastoma cells. Cancers. 2019 Jun 1;11(6). 747. https://doi.org/10.3390/cancers11060747
Colucci-D’amato, Luca ; Pastorino, Olga ; Teresa Gentile, Maria ; Mancini, Alessandro ; Del Gaudio, Nunzio ; Di Costanzo, Antonella ; Bajetto, Adriana ; Franco, Paola ; Altucci, Lucia ; Florio, Tullio ; Patrizia Stoppelli, Maria. / Histone deacetylase inhibitors impair vasculogenic mimicry from glioblastoma cells. In: Cancers. 2019 ; Vol. 11, No. 6.
@article{df55e0967d4048728156d827517c613a,
title = "Histone deacetylase inhibitors impair vasculogenic mimicry from glioblastoma cells",
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{\circledR}, 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.",
keywords = "Angiogenesis, Cancer stem cells, Cell invasion, Cell migration, Glioblastoma, HDAC, Vasculogenic mimicry",
author = "Luca Colucci-D’amato and Olga Pastorino and {Teresa Gentile}, Maria and Alessandro Mancini and {Del Gaudio}, Nunzio and {Di Costanzo}, Antonella and Adriana Bajetto and Paola Franco and Lucia Altucci and Tullio Florio and {Patrizia Stoppelli}, Maria",
year = "2019",
month = "6",
day = "1",
doi = "10.3390/cancers11060747",
language = "English",
volume = "11",
journal = "Cancers",
issn = "2072-6694",
publisher = "MDPI AG",
number = "6",

}

TY - JOUR

T1 - Histone deacetylase inhibitors impair vasculogenic mimicry from glioblastoma cells

AU - Colucci-D’amato, Luca

AU - Pastorino, Olga

AU - Teresa Gentile, Maria

AU - Mancini, Alessandro

AU - Del Gaudio, Nunzio

AU - Di Costanzo, Antonella

AU - Bajetto, Adriana

AU - Franco, Paola

AU - Altucci, Lucia

AU - Florio, Tullio

AU - Patrizia Stoppelli, Maria

PY - 2019/6/1

Y1 - 2019/6/1

N2 - 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.

AB - 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.

KW - Angiogenesis

KW - Cancer stem cells

KW - Cell invasion

KW - Cell migration

KW - Glioblastoma

KW - HDAC

KW - Vasculogenic mimicry

UR - http://www.scopus.com/inward/record.url?scp=85069535648&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85069535648&partnerID=8YFLogxK

U2 - 10.3390/cancers11060747

DO - 10.3390/cancers11060747

M3 - Article

AN - SCOPUS:85069535648

VL - 11

JO - Cancers

JF - Cancers

SN - 2072-6694

IS - 6

M1 - 747

ER -