Speaker
Description
Glioblastoma (GBM) is an aggressive and highly heterogeneous brain tumor, making treatment development particularly challenging. A key contributor to GBM's heterogeneity is glioblastoma stem cells (GSCs), which possess critical properties such as self-renewal, plasticity, and resistance to therapy. These characteristics are pivotal in tumor progression and recurrence, highlighting the need for a deeper understanding of GSC stemness mechanisms to improve therapeutic strategies. GBM cells utilize neurodevelopmental pathways, and GSCs share transcriptomic similarities with neural stem cells, particularly basal or outer radial glia (bRG). These bRG-like cells exhibit morphological diversity, which is thought to regulate cellular processes like proliferation and migration. Our recent research suggests that GSC morphology is strongly associated with their functional properties, leading us to investigate this further.
Using patient-derived 2D and 3D in vitro models, we identified GSC morphology as a novel and significant aspect of GSC heterogeneity. While bRG cells are categorized by number of cellular protrusions, GSCs displayed a much broader range of morphological variation both between and within individual patients. Specifically, GSCs exhibited differences in protrusion length, thickness, cell-cell network formation, and overall cell flatness. Based on these morphological features, we classified GSCs into distinct morpho-classes, which displayed different self-renewal potential in vitro. Transcriptomic profiling revealed that morpho-classes with higher clonogenic potential were enriched in molecular pathways related to tumor growth and aggressiveness. These pathways are also involved in neurodevelopmental processes, such as maintaining bRG cell properties, promoting neuronal process growth, and morphogenesis.
In conclusion, our study demonstrates that GSC morphology and stemness are intricately linked, likely through neurodevelopmental morphoregulatory pathways. These findings open the door to targeting morphoregulators as a potential therapeutic strategy to limit GBM aggressiveness.
| Author(s) | Stefania Faletti*, Giulia Scotti, Negin Alizadehmohajer, Alberto Campione, Carlotta Barelli, Roberta Bosotti, Roberto Stefini, Nereo Kalebic |
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| Affiliation(s) | Human Technopole, Human Technopole, Human Technopole, Neurosurgery Unit - ASST Ovest Milanese - Legnano Hospital – Legnano - Italy, Human Technopole, Human Technopole, Neurosurgery Unit - ASST Ovest Milanese - Legnano Hospital – Legnano - Italy, Human Technopole |
