ArticleJournal of neuro-oncology2025
Three-dimensional ultrastructural analysis of glioblastoma reveals spheresome-mediated intercellular communication.
Article in Journal of neuro-oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
purposeThe tumor microenvironment plays a central role in glioblastoma progression and treatment resistance, with extracellular vesicles (EVs) mediating much of the intercellular communication. Here, we provide the first ultrastructural evidence of spheresomes -a specific EV subtype- predominance in human glioblastomas, together with novel observations on their transport and interactions.
methodsTumor samples from four patients with histologically confirmed glioblastoma were examined using transmission electron microscopy (TEM) and three-dimensional (3D) reconstructions from ultrathin serial sections.
resultsIn glioblastomas, spheresomes, contained within multivesicular spheres (MVSs), were the most prevalent EV subtype, exceeding multivesicular bodies containing exosomes in number and size. 3D reconstructions revealed numerous contacts between glioblastoma tumor cells and MVSs, active release events, and occasional traversal of endothelial cells into the vascular lumen, suggesting potential for both local and systemic transport. Additionally, we report independent and descriptive new ultrastructural observations of glioblastoma. These tumors well-differenciated cells exhibited irregular nuclei with nuclear blebs and nuclear envelope-limited chromatin sheets, as well as cytoplasmic concentric rough endoplasmic reticulum laminations, membranous stacks, crystalline bodies, and concentric rearrangements of gliofilaments. Primary cilia (9 + 0) were also observed.
conclusionsThese findings expand the ultrastructural profile of glioblastoma, highlight spheresomes as a potentially important EV population in tumor communication, and underscore the value of further molecular studies to evaluate their role as potential biomarkers.
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