A vascularized tumoroid model for human glioblastoma angiogenesis.

Autor: Tatla AS; Department of Engineering, University of Cambridge, Trumpington Street, Cambridge, CB2 1PZ, UK. as2307@cam.ac.uk., Justin AW; Department of Engineering, University of Cambridge, Trumpington Street, Cambridge, CB2 1PZ, UK., Watts C; Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Addenbrooke's Hospital, Cambridge, CB2 0QQ, UK.; Institute of Cancer and Genomic Sciences, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK., Markaki AE; Department of Engineering, University of Cambridge, Trumpington Street, Cambridge, CB2 1PZ, UK. am253@cam.ac.uk.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2021 Oct 01; Vol. 11 (1), pp. 19550. Date of Electronic Publication: 2021 Oct 01.
DOI: 10.1038/s41598-021-98911-y
Abstrakt: 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.
(© 2021. The Author(s).)
Databáze: MEDLINE
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