Defining tumor-associated vascular heterogeneity in pediatric high-grade and diffuse midline gliomas

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...

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Bibliographic Details
Published in:Acta neuropathologica communications 2021-08, Vol.9 (1), p.142-142, Article 142
Main Authors: Wei, Xin, Meel, Michaël H, Breur, Marjolein, Bugiani, Marianna, Hulleman, Esther, Phoenix, Timothy N
Format: Article
Language:English
Subjects:
Animals
Antibodies
Blood brain barrier
Blood-Brain Barrier - pathology
Brain - blood supply
Brain - pathology
Brain cancer
Brain Neoplasms - pathology
Brain tumors
Child
Diffuse intrinsic pontine glioma
Diffuse midline glioma
Endothelial cells
Glioma
Glioma - pathology
Gliomas
Histology
Humans
Mice
Mice, Inbred NOD
Mice, SCID
Mutation
Neoplasm Grading - methods
Neurovascular Coupling - physiology
Neurovascular unit
Pediatric high-grade glioma
Pediatrics
Plasmids
Tumors
Xenograft Model Antitumor Assays - methods
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Summary: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.
ISSN:2051-5960
2051-5960
DOI:10.1186/s40478-021-01243-1