Defining tumor-associated vascular heterogeneity in pediatric high-grade and diffuse midline gliomas
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-gra...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2021-08-01
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| Series: | Acta Neuropathologica Communications |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s40478-021-01243-1 |
| _version_ | 1818601125902811136 |
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| author | Xin Wei Michaël H. Meel Marjolein Breur Marianna Bugiani Esther Hulleman Timothy N. Phoenix |
| author_facet | Xin Wei Michaël H. Meel Marjolein Breur Marianna Bugiani Esther Hulleman Timothy N. Phoenix |
| author_sort | Xin Wei |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-16T12:46:25Z |
| format | Article |
| id | doaj.art-577c7abe343a43c39671695146a4f1f4 |
| institution | Directory Open Access Journal |
| issn | 2051-5960 |
| language | English |
| last_indexed | 2024-12-16T12:46:25Z |
| publishDate | 2021-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Acta Neuropathologica Communications |
| spelling | doaj.art-577c7abe343a43c39671695146a4f1f42022-12-21T22:31:17ZengBMCActa Neuropathologica Communications2051-59602021-08-019111810.1186/s40478-021-01243-1Defining tumor-associated vascular heterogeneity in pediatric high-grade and diffuse midline gliomasXin Wei0Michaël H. Meel1Marjolein Breur2Marianna Bugiani3Esther Hulleman4Timothy N. Phoenix5Division of Pharmaceutical Sciences, James L. Winkle College of Pharmacy, University of CincinnatiPrincess Máxima Center for Pediatric OncologyAmsterdam Leukodystrophy Center, Amsterdam UMCDepartment of Pathology, Amsterdam UMC, Vrije Universiteit Amsterdam and Amsterdam NeurosciencePrincess Máxima Center for Pediatric OncologyDivision of Pharmaceutical Sciences, James L. Winkle College of Pharmacy, University of CincinnatiAbstract 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.https://doi.org/10.1186/s40478-021-01243-1Pediatric high-grade gliomaDiffuse midline gliomaBlood brain barrierEndothelial cellsNeurovascular unitDiffuse intrinsic pontine glioma |
| spellingShingle | Xin Wei Michaël H. Meel Marjolein Breur Marianna Bugiani Esther Hulleman Timothy N. Phoenix Defining tumor-associated vascular heterogeneity in pediatric high-grade and diffuse midline gliomas Acta Neuropathologica Communications Pediatric high-grade glioma Diffuse midline glioma Blood brain barrier Endothelial cells Neurovascular unit Diffuse intrinsic pontine glioma |
| title | Defining tumor-associated vascular heterogeneity in pediatric high-grade and diffuse midline gliomas |
| title_full | Defining tumor-associated vascular heterogeneity in pediatric high-grade and diffuse midline gliomas |
| title_fullStr | Defining tumor-associated vascular heterogeneity in pediatric high-grade and diffuse midline gliomas |
| title_full_unstemmed | Defining tumor-associated vascular heterogeneity in pediatric high-grade and diffuse midline gliomas |
| title_short | Defining tumor-associated vascular heterogeneity in pediatric high-grade and diffuse midline gliomas |
| title_sort | defining tumor associated vascular heterogeneity in pediatric high grade and diffuse midline gliomas |
| topic | Pediatric high-grade glioma Diffuse midline glioma Blood brain barrier Endothelial cells Neurovascular unit Diffuse intrinsic pontine glioma |
| url | https://doi.org/10.1186/s40478-021-01243-1 |
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