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Pacioni S, D'Alessandris QG, Buccarelli M, et al. Brain Invasion along Perivascular Spaces by Glioma Cells: Relationship with Blood-Brain Barrier. Cancers (Basel). 2019;12(1)doi: 10.3390/cancers12010018.
Pacioni, S., D'Alessandris, Q. G., Buccarelli, M., Boe, A., Martini, M., Larocca, L. M., Bolasco, G., Ricci-Vitiani, L., Falchetti, M. L., & Pallini, R. (2019). Brain Invasion along Perivascular Spaces by Glioma Cells: Relationship with Blood-Brain Barrier. Cancers, 12(1), . https://doi.org/10.3390/cancers12010018
Pacioni, Simone, et al. "Brain Invasion along Perivascular Spaces by Glioma Cells: Relationship with Blood-Brain Barrier." Cancers vol. 12,1 (2019). doi: https://doi.org/10.3390/cancers12010018
Pacioni S, D'Alessandris QG, Buccarelli M, Boe A, Martini M, Larocca LM, Bolasco G, Ricci-Vitiani L, Falchetti ML, Pallini R. Brain Invasion along Perivascular Spaces by Glioma Cells: Relationship with Blood-Brain Barrier. Cancers (Basel). 2019 Dec 19;12(1). doi: 10.3390/cancers12010018. PMID: 31861603; PMCID: PMC7017006.
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Cancers (Basel). 2019 Dec 19;12(1). doi: 10.3390/cancers12010018.

Brain Invasion along Perivascular Spaces by Glioma Cells: Relationship with Blood-Brain Barrier.

Cancers

Simone Pacioni, Quintino Giorgio D'Alessandris, Mariachiara Buccarelli, Alessandra Boe, Maurizio Martini, Luigi Maria Larocca, Giulia Bolasco, Lucia Ricci-Vitiani, Maria Laura Falchetti, Roberto Pallini

Affiliations

  1. Institute of Neurosurgery, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, 00168 Rome, Italy.
  2. CNR-IBBC, Institute of Biochemistry and Cell Biology, 00015 Rome, Italy.
  3. Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, 0161 Rome, Italy.
  4. Core Facilities, Istituto Superiore di Sanità, 00161 Rome, Italy.
  5. Institute of Human Pathology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, 00168 Rome, Italy.
  6. Epigenetics & Neurobiology Unit, European Molecular Biology Laboratory (EMBL Rome), 00015 Monterotondo, Italy.

PMID: 31861603 PMCID: PMC7017006 DOI: 10.3390/cancers12010018

Abstract

The question whether perivascular glioma cells invading the brain far from the tumor bulk may disrupt the blood-brain barrier (BBB) represents a crucial issue because under this condition tumor cells would be no more protected from the reach of chemotherapeutic drugs. A recent in vivo study that used human xenolines, demonstrated that single glioma cells migrating away from the tumor bulk are sufficient to breach the BBB. Here, we used brain xenografts of patient-derived glioma stem-like cells (GSCs) to show by immunostaining that in spite of massive perivascular invasion, BBB integrity was preserved in the majority of vessels located outside the tumor bulk. Interestingly, the tumor cells that invaded the brain for the longest distances traveled along vessels with retained BBB integrity. In surgical specimens of malignant glioma, the area of brain invasion showed several vessels with preserved BBB that were surrounded by tumor cells. On transmission electron microscopy, the cell inter-junctions and basal lamina of the brain endothelium were preserved even in conditions in which the tumor cells lay adjacently to blood vessels. In conclusion, BBB integrity associates with extensive perivascular invasion of glioma cells.

Keywords: blood–brain barrier; brain endothelium; glioblastoma; glioma stem-like cells; perivascular invasion

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