Senior Scientist Central Institute of Mental Health Mannheim, Germany
Abstract: In glioblastoma (GBM) the intricate interplay between tumor cells and the surrounding microenvironment plays a crucial role in tumor progression, invasion, and therapeutic resistance. So far, studying these interactions in a controlled and representative model system has been challenging. Here, we present the development of hGliCS, a human glioma-cortical spheroid model that allows the elucidation of the biology of GBM cells and their interactions with a human-specific brain-like microenvironment and neurons. GBM cells efficiently invade the cortical spheroids, forming a well-connected network of communicating cells. The heterogeneous cellular states of the GBM cells within this model closely resembled findings previously observed in glioblastoma patients and in mouse xenografts. In contrast to the substantial changes observed in the tumor cell population, the impact of the GBM cells on the neurons was minimal. Finally, we further demonstrate the suitability of hGliCS to test and validate compounds targeting tumor-specific neurobiological features, which could easily be adapted to high-throughput conditions.