A brain cancer microtissue model for studying tumor cell and neural cell interactions

Glioblastoma (GBM) is an aggressive brain cancer with a poor prognosis and is challenging to study due to its high degree of inter- and intra-tumoral heterogeneity and complex tumor microenvironment. Current in vitro models of GBM, including patient-derived organoids and 2D and 3D cell cultures can recapitulate aspects of the GBM biology, but interactions with normal cells of the central nervous system remain challenging to model. Herein, we introduce a new 3D biomimetic brain cancer microtissue (BCM) developed by co-culturing rat cortical microtissues with rat glioma cell lines. Leveraging this model, we have characterized glioma cell motility, invasiveness, and interactions with neurons, astrocytes, and microglia. GBM cell behavior in the BCM model is consistent with that observed in vivo. This robust and versatile platform will enable future high-throughput therapeutic screening and detailed insights into primary glioma biology and potentially other brain tumors and cancers that metastasize to the brain.