Defining tumor-associated vascular heterogeneity in pediatric high-grade and diffuse midline gliomas.
Acta Neuropathol Commun
; 9(1): 142, 2021 08 23.
Article
en En
| MEDLINE
| ID: mdl-34425907
ABSTRACT
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Encéfalo
/
Neoplasias Encefálicas
/
Ensayos Antitumor por Modelo de Xenoinjerto
/
Acoplamiento Neurovascular
/
Glioma
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Límite:
Animals
/
Child
/
Humans
Idioma:
En
Revista:
Acta Neuropathol Commun
Año:
2021
Tipo del documento:
Article
País de afiliación:
Estados Unidos