A vascularized tumoroid model for human glioblastoma angiogenesis

Abstract Glioblastoma (GBM) angiogenesis is critical for tumor growth and recurrence, making it a compelling therapeutic target. Here, a disease-relevant, vascularized tumoroid in vitro model with stem-like features and stromal surrounds is reported. The model is used to recapitulate how individual...

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Autores principales:	Agavi Stavropoulou Tatla, Alexander W. Justin, Colin Watts, Athina E. Markaki
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2a6e5c25be114acba644f4ae7b071551
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spelling	oai:doaj.org-article:2a6e5c25be114acba644f4ae7b0715512021-12-02T18:51:14ZA vascularized tumoroid model for human glioblastoma angiogenesis10.1038/s41598-021-98911-y2045-2322https://doaj.org/article/2a6e5c25be114acba644f4ae7b0715512021-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-98911-yhttps://doaj.org/toc/2045-2322Abstract Glioblastoma (GBM) angiogenesis is critical for tumor growth and recurrence, making it a compelling therapeutic target. Here, a disease-relevant, vascularized tumoroid in vitro model with stem-like features and stromal surrounds is reported. The model is used to recapitulate how individual components of the GBM’s complex brain microenvironment such as hypoxia, vasculature-related stromal cells and growth factors support GBM angiogenesis. It is scalable, tractable, cost-effective and can be used with biologically-derived or biomimetic matrices. Patient-derived primary GBM cells are found to closely participate in blood vessel formation in contrast to a GBM cell line containing differentiated cells. Exogenous growth factors amplify this effect under normoxia but not at hypoxia suggesting that a significant amount of growth factors is already being produced under hypoxic conditions. Under hypoxia, primary GBM cells strongly co-localize with umbilical vein endothelial cells to form sprouting vascular networks, which has been reported to occur in vivo. These findings demonstrate that our 3D tumoroid in vitro model exhibits biomimetic attributes that may permit its use as a preclinical model in studying microenvironment cues of tumor angiogenesis.Agavi Stavropoulou TatlaAlexander W. JustinColin WattsAthina E. MarkakiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Agavi Stavropoulou Tatla Alexander W. Justin Colin Watts Athina E. Markaki A vascularized tumoroid model for human glioblastoma angiogenesis
description	Abstract Glioblastoma (GBM) angiogenesis is critical for tumor growth and recurrence, making it a compelling therapeutic target. Here, a disease-relevant, vascularized tumoroid in vitro model with stem-like features and stromal surrounds is reported. The model is used to recapitulate how individual components of the GBM’s complex brain microenvironment such as hypoxia, vasculature-related stromal cells and growth factors support GBM angiogenesis. It is scalable, tractable, cost-effective and can be used with biologically-derived or biomimetic matrices. Patient-derived primary GBM cells are found to closely participate in blood vessel formation in contrast to a GBM cell line containing differentiated cells. Exogenous growth factors amplify this effect under normoxia but not at hypoxia suggesting that a significant amount of growth factors is already being produced under hypoxic conditions. Under hypoxia, primary GBM cells strongly co-localize with umbilical vein endothelial cells to form sprouting vascular networks, which has been reported to occur in vivo. These findings demonstrate that our 3D tumoroid in vitro model exhibits biomimetic attributes that may permit its use as a preclinical model in studying microenvironment cues of tumor angiogenesis.
format	article
author	Agavi Stavropoulou Tatla Alexander W. Justin Colin Watts Athina E. Markaki
author_facet	Agavi Stavropoulou Tatla Alexander W. Justin Colin Watts Athina E. Markaki
author_sort	Agavi Stavropoulou Tatla
title	A vascularized tumoroid model for human glioblastoma angiogenesis
title_short	A vascularized tumoroid model for human glioblastoma angiogenesis
title_full	A vascularized tumoroid model for human glioblastoma angiogenesis
title_fullStr	A vascularized tumoroid model for human glioblastoma angiogenesis
title_full_unstemmed	A vascularized tumoroid model for human glioblastoma angiogenesis
title_sort	vascularized tumoroid model for human glioblastoma angiogenesis
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/2a6e5c25be114acba644f4ae7b071551
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_version_	1718377435822555136

A vascularized tumoroid model for human glioblastoma angiogenesis

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