Three-dimensional vascular microenvironment landscape in human glioblastoma

The cellular complexity of glioblastoma microenvironments is still poorly understood. In-depth, cell-resolution tissue analyses of human material are rare but highly necessary to understand the biology of this deadly tumor. Here we present a unique 3D visualization revealing the cellular composition...

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Detalhes bibliográficos
Autores: Cribaro, George Paul|||0000-0002-5251-1537, Saavedra-López, Elena|||0000-0001-9788-2414, Romarate, Leire, Mitxitorena, Izaskun, Díaz, Laura R., Casanova, Paola|||0000-0002-4814-0577, Roig-Martínez, Meritxell, Gallego, José Maria, Perez-Vallés, Ana, Barcia, Carlos|||0000-0003-0976-4245
Formato: artículo
Fecha de publicación:2021
País:España
Recursos:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:236923
Acesso em linha:https://ddd.uab.cat/record/236923
https://dx.doi.org/urn:doi:10.1186/s40478-020-01115-0
Access Level:acceso abierto
Palavra-chave:Glioblastoma
Blood vessels
Microglia
Macrophages
Astrocytes
T cells
Endothelium
Basement membrane
Tumor microenvironments
Descrição
Resumo:The cellular complexity of glioblastoma microenvironments is still poorly understood. In-depth, cell-resolution tissue analyses of human material are rare but highly necessary to understand the biology of this deadly tumor. Here we present a unique 3D visualization revealing the cellular composition of human GBM in detail and considering its critical association with the neo-vascular niche. Our images show a complex vascular map of human 3D biopsies with increased vascular heterogeneity and altered spatial relationship with astrocytes or glioma-cell counterparts. High-resolution analysis of the structural layers of the blood brain barrier showed a multilayered fenestration of endothelium and basement membrane. Careful examination of T cell position and migration relative to vascular walls revealed increased infiltration corresponding with tumor proliferation. In addition, the analysis of the myeloid landscape not only showed a volumetric increase in glioma-associated microglia and macrophages relative to GBM proliferation but also revealed distinct phenotypes in tumor nest and stroma. Images and data sets are available on demand as a resource for public access.