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

Xin Wei, Michael H. Meel, Marjolein Breur, Marianna Bugiani, Esther Hulleman, Timothy N. Phoenix

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

14 Citaten (Scopus)


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.
Originele taal-2Engels
Pagina's (van-tot)142
TijdschriftActa Neuropathologica Communications
Nummer van het tijdschrift1
StatusGepubliceerd - 23 aug. 2021


  • Pediatric high-grade glioma
  • Diffuse midline glioma
  • Blood brain barrier
  • Endothelial cells
  • Neurovascular unit
  • Diffuse intrinsic pontine glioma
  • H3K27M
  • Wnt signaling

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