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.
Glioblastoma (GBM) angiogenesis is critical for the tumor's fast growth and recurrence. Here, we report a biomimetic, in vitro vascularized tumoroid model with stromal surrounds. This 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. Patient-derived primary GBM cells were found to participate in blood vessel formation. Exogenous growth factors amplified this effect under normoxia but not under hypoxia suggesting that hypoxic GBM cells are already producing a significant amount of growth factors. Primary GBM cells showed a stronger angiogenic potential when compared to a GBM cell line containing differentiated cells. Under hypoxia, primary GBM cells and umbilical vein endothelial cells were found to strongly co-localize with GBM cells acquiring an endothelial-like behaviour, which has been reported to occur in vivo. These findings demonstrate that our in vitro tumoroid model exhibits biomimetic attributes that may permit its use in studying microenvironment cues of tumor angiogenesis.
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