Spatiotemporal Insights into Glioma Oncostream Dynamics: Unraveling Formation, Stability, and Disassembly Pathways.

ABSTRACT

Glioblastoma (GBM) remains a challenge in Neuro-oncology, with a poor prognosis showing only a 5% survival rate beyond two years. This is primarily due to its aggressiveness and intra-tumoral heterogeneity, which limits complete surgical resection and reduces the efficacy of existing treatments. The existence of oncostreams-neuropathological structures comprising aligned spindle-like cells from both tumor and non-tumor origins- is discovered earlier. Oncostreams are closely linked to glioma aggressiveness and facilitate the spread into adjacent healthy brain tissue. A unique molecular signature intrinsic to oncostreams, with overexpression of key genes (i.e., COL1A1, ACTA2) that drive the tumor's mesenchymal transition and malignancy is also identified. Pre-clinical studies on genetically engineered mouse models demonstrated that COL1A1 inhibition disrupts oncostreams, modifies TME, reduces mesenchymal gene expression, and extends survival. An in vitro model using GFP+ NPA cells to investigate how various treatments affect oncostream dynamics is developed. Analysis showed that factors such as cell density, morphology, neurotransmitter agonists, calcium chelators, and cytoskeleton-targeting drugs influence oncostream formation. This data illuminate the patterns of glioma migration and suggest anti-invasion strategies that can improve GBM patient outcomes when combined with traditional therapies. This work highlights the potential of targeting oncostreams to control glioma invasion and enhance treatment efficacy.