PMID- 34425907
OWN - NLM
STAT- MEDLINE
DCOM- 20220124
LR  - 20220124
IS  - 2051-5960 (Electronic)
IS  - 2051-5960 (Linking)
VI  - 9
IP  - 1
DP  - 2021 Aug 23
TI  - Defining tumor-associated vascular heterogeneity in pediatric high-grade and 
      diffuse midline gliomas.
PG  - 142
LID - 10.1186/s40478-021-01243-1 [doi]
LID - 142
AB  - 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.
CI  - (c) 2021. The Author(s).
FAU - Wei, Xin
AU  - Wei X
AD  - Division of Pharmaceutical Sciences, James L. Winkle College of Pharmacy, 
      University of Cincinnati, Cincinnati, OH, USA.
FAU - Meel, Michael H
AU  - Meel MH
AD  - Princess Maxima Center for Pediatric Oncology, Utrecht, the Netherlands.
AD  - Department of Pediatric Oncology/Hematology, Cancer Center Amsterdam, VU 
      University Medical Center, Amsterdam, the Netherlands.
FAU - Breur, Marjolein
AU  - Breur M
AD  - Amsterdam Leukodystrophy Center, Amsterdam UMC, Amsterdam, The Netherlands.
AD  - Department of Child Neurology, Emma Children's Hospital, Amsterdam UMC, Vrije 
      Universiteit Amsterdam and Amsterdam Neuroscience, Amsterdam, The Netherlands.
FAU - Bugiani, Marianna
AU  - Bugiani M
AD  - Department of Pathology, Amsterdam UMC, Vrije Universiteit Amsterdam and 
      Amsterdam Neuroscience, de Boelelaan 1117, 1081HV, Amsterdam, The Netherlands.
AD  - Amsterdam Leukodystrophy Center, Amsterdam UMC, Amsterdam, The Netherlands.
FAU - Hulleman, Esther
AU  - Hulleman E
AD  - Princess Maxima Center for Pediatric Oncology, Utrecht, the Netherlands.
AD  - Department of Pediatric Oncology/Hematology, Cancer Center Amsterdam, VU 
      University Medical Center, Amsterdam, the Netherlands.
FAU - Phoenix, Timothy N
AU  - Phoenix TN
AUID- ORCID: 0000-0003-4771-4003
AD  - Division of Pharmaceutical Sciences, James L. Winkle College of Pharmacy, 
      University of Cincinnati, Cincinnati, OH, USA. timothy.phoenix@uc.edu.
AD  - Research in Patient Services, Cincinnati Children's Hospital Medical Center, 
      Cincinnati, OH, USA. timothy.phoenix@uc.edu.
LA  - eng
GR  - P30 ES006096/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20210823
PL  - England
TA  - Acta Neuropathol Commun
JT  - Acta neuropathologica communications
JID - 101610673
SB  - IM
MH  - Animals
MH  - Blood-Brain Barrier/pathology
MH  - Brain/*blood supply/*pathology
MH  - Brain Neoplasms/*pathology
MH  - Child
MH  - Glioma/*pathology
MH  - Humans
MH  - Mice
MH  - Mice, Inbred NOD
MH  - Mice, SCID
MH  - Neoplasm Grading/methods
MH  - *Neurovascular Coupling/physiology
MH  - Xenograft Model Antitumor Assays/*methods
PMC - PMC8381557
OTO - NOTNLM
OT  - Blood brain barrier
OT  - Diffuse intrinsic pontine glioma
OT  - Diffuse midline glioma
OT  - Endothelial cells
OT  - H3K27M
OT  - Neurovascular unit
OT  - Pediatric high-grade glioma
OT  - Wnt signaling
COIS- The authors declare that they have no competing interests.
EDAT- 2021/08/25 06:00
MHDA- 2022/01/27 06:00
PMCR- 2021/08/23
CRDT- 2021/08/24 05:35
PHST- 2021/07/02 00:00 [received]
PHST- 2021/08/10 00:00 [accepted]
PHST- 2021/08/24 05:35 [entrez]
PHST- 2021/08/25 06:00 [pubmed]
PHST- 2022/01/27 06:00 [medline]
PHST- 2021/08/23 00:00 [pmc-release]
AID - 10.1186/s40478-021-01243-1 [pii]
AID - 1243 [pii]
AID - 10.1186/s40478-021-01243-1 [doi]
PST - epublish
SO  - Acta Neuropathol Commun. 2021 Aug 23;9(1):142. doi: 10.1186/s40478-021-01243-1.