Glioblastoma disrupts the ependymal wall and extracellular matrix structures of the subventricular zone.

Autor: Norton ES; Department of Neurosurgery, Mayo Clinic Florida, 4500 San Pablo Road, Jacksonville, FL, 32224, USA.; Neuroscience Graduate Program, Mayo Clinic Graduate School of Biomedical Sciences, Mayo Clinic, Jacksonville, FL, USA.; Regenerative Sciences Training Program, Center for Regenerative Medicine, Mayo Clinic, Jacksonville, FL, USA., Whaley LA; Department of Neurosurgery, Mayo Clinic Florida, 4500 San Pablo Road, Jacksonville, FL, 32224, USA.; Department of Biology, University of North Florida, Jacksonville, FL, USA., Ulloa-Navas MJ; Laboratory of Comparative Neurobiology, Cavanilles Institute of Biodiversity and Evolutionary Biology, University of Valencia, CIBERNED, Paterna, Spain.; Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA., García-Tárraga P; Laboratory of Comparative Neurobiology, Cavanilles Institute of Biodiversity and Evolutionary Biology, University of Valencia, CIBERNED, Paterna, Spain., Meneses KM; Department of Cancer Biology, Mayo Clinic, Jacksonville, FL, USA.; Biochemistry and Molecular Biology Graduate Program, Mayo Clinic Graduate School of Biomedical Sciences, Mayo Clinic, Jacksonville, FL, USA., Lara-Velazquez M; Department of Neurosurgery, Mayo Clinic Florida, 4500 San Pablo Road, Jacksonville, FL, 32224, USA., Zarco N; Department of Neurosurgery, Mayo Clinic Florida, 4500 San Pablo Road, Jacksonville, FL, 32224, USA., Carrano A; Department of Neurosurgery, Mayo Clinic Florida, 4500 San Pablo Road, Jacksonville, FL, 32224, USA., Quiñones-Hinojosa A; Department of Neurosurgery, Mayo Clinic Florida, 4500 San Pablo Road, Jacksonville, FL, 32224, USA., García-Verdugo JM; Laboratory of Comparative Neurobiology, Cavanilles Institute of Biodiversity and Evolutionary Biology, University of Valencia, CIBERNED, Paterna, Spain., Guerrero-Cázares H; Department of Neurosurgery, Mayo Clinic Florida, 4500 San Pablo Road, Jacksonville, FL, 32224, USA. Guerrero-Cazares.Hugo@mayo.edu.
Jazyk: angličtina
Zdroj: Fluids and barriers of the CNS [Fluids Barriers CNS] 2022 Jul 11; Vol. 19 (1), pp. 58. Date of Electronic Publication: 2022 Jul 11.
DOI: 10.1186/s12987-022-00354-8
Abstrakt: Background: Glioblastoma (GBM) is the most aggressive and common type of primary brain tumor in adults. Tumor location plays a role in patient prognosis, with tumors proximal to the lateral ventricles (LVs) presenting with worse overall survival, increased expression of stem cell genes, and increased incidence of distal tumor recurrence. This may be due in part to interaction of GBM with factors of the subventricular zone (SVZ), including those contained within the cerebrospinal fluid (CSF). However, direct interaction of GBM tumors with CSF has not been proved and would be hindered in the presence of an intact ependymal cell layer.
Methods: Here, we investigate the ependymal cell barrier and its derived extracellular matrix (ECM) fractones in the vicinity of a GBM tumor. Patient-derived GBM cells were orthotopically implanted into immunosuppressed athymic mice in locations distal and proximal to the LV. A PBS vehicle injection in the proximal location was included as a control. At four weeks post-xenograft, brain tissue was examined for alterations in ependymal cell health via immunohistochemistry, scanning electron microscopy, and transmission electron microscopy.
Results: We identified local invading GBM cells within the LV wall and increased influx of CSF into the LV-proximal GBM tumor bulk compared to controls. In addition to the physical disruption of the ependymal cell barrier, we also identified increased signs of compromised ependymal cell health in LV-proximal tumor-bearing mice. These signs include increased accumulation of lipid droplets, decreased cilia length and number, and decreased expression of cell channel proteins. We additionally identified elevated numbers of small fractones in the SVZ within this group, suggesting increased indirect CSF-contained molecule signaling to tumor cells.
Conclusions: Our data is the first to show that LV-proximal GBMs physically disrupt the ependymal cell barrier in animal models, resulting in disruptions in ependymal cell biology and increased CSF interaction with the tumor bulk. These findings point to ependymal cell health and CSF-contained molecules as potential axes for therapeutic targeting in the treatment of GBM.
(© 2022. The Author(s).)
Databáze: MEDLINE
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