Defining tumor-associated vascular heterogeneity in pediatric high-grade and diffuse midline gliomas.
Blood brain barrier
Diffuse intrinsic pontine glioma
Diffuse midline glioma
Endothelial cells
H3K27M
Neurovascular unit
Pediatric high-grade glioma
Wnt signaling
Journal
Acta neuropathologica communications
ISSN: 2051-5960
Titre abrégé: Acta Neuropathol Commun
Pays: England
ID NLM: 101610673
Informations de publication
Date de publication:
23 08 2021
23 08 2021
Historique:
received:
02
07
2021
accepted:
10
08
2021
entrez:
24
8
2021
pubmed:
25
8
2021
medline:
27
1
2022
Statut:
epublish
Résumé
The blood-brain barrier (BBB) plays important roles in brain tumor pathogenesis and treatment response, yet our understanding of its function and heterogeneity within or across brain tumor types remains poorly characterized. Here we analyze the neurovascular unit (NVU) of pediatric high-grade glioma (pHGG) and diffuse midline glioma (DMG) using patient derived xenografts and natively forming glioma mouse models. We show tumor-associated vascular differences between these glioma subtypes, and parallels between PDX and mouse model systems, with DMG models maintaining a more normal vascular architecture, BBB function and endothelial transcriptional program relative to pHGG models. Unlike prior work in angiogenic brain tumors, we find that expression of secreted Wnt antagonists do not alter the tumor-associated vascular phenotype in DMG tumor models. Together, these findings highlight vascular heterogeneity between pHGG and DMG and differences in their response to alterations in developmental BBB signals that may participate in driving these pathological differences.
Identifiants
pubmed: 34425907
doi: 10.1186/s40478-021-01243-1
pii: 10.1186/s40478-021-01243-1
pmc: PMC8381557
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
142Subventions
Organisme : NIEHS NIH HHS
ID : P30 ES006096
Pays : United States
Informations de copyright
© 2021. The Author(s).
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