Journal
SLAS DISCOVERY
Volume 23, Issue 8, Pages 862-868Publisher
SAGE PUBLICATIONS INC
DOI: 10.1177/2472555218764623
Keywords
three-dimensional cellular assay; hybrid compartment organoids; brain tumor cell migration; glioblastoma stem-cell-like cells
Funding
- MRC New Investigator Award [MR/J001171/1]
- Brain Tumor Research and Support across Yorkshire
- Leeds Cancer Research UK Centre
- MRC [MR/J001171/1] Funding Source: UKRI
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Organoid methodology provides a platform for the ex vivo investigation of the cellular and molecular mechanisms underlying brain development and disease. The high-grade brain tumor glioblastoma multiforme (GBM) is considered a cancer of unmet clinical need, in part due to GBM cell infiltration into healthy brain parenchyma, making complete surgical resection improbable. Modeling the process of GBM invasion in real time is challenging as it requires both tumor and neural tissue compartments. Here, we demonstrate that human GBM spheroids possess the ability to spontaneously infiltrate early-stage cerebral organoids (eCOs). The resulting formation of hybrid organoids demonstrated an invasive tumor phenotype that was distinct from noncancerous adult neural progenitor (NP) spheroid incorporation into eCOs. These findings provide a basis for the modeling and quantification of the GBM infiltration process using a stem-cell-based organoid approach, and may be used for the identification of anti-GBM invasion strategies.
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