Search

Microglial cells represent the resident immune elements of the central nervous system, where they exert constant monitoring and contribute to preserving neuronal activity and function. In the context of glioblastoma (GBM), a common type of tumor originating in the brain, microglial cells deeply modify their phenotype, lose their homeostatic functions, invade the tumoral mass and support the growth and further invasion of the tumoral cells into the surrounding brain parenchyma. These modifications are, at least in part, induced by bidirectional communication among microglial and tumoral cells through the release of soluble molecules and extracellular vesicles (EVs). EVs produced by GBM and microglial cells transfer different kinds of biological information to receiving cells, deeply modifying their phenotype and activity and could represent important diagnostic markers and therapeutic targets. Recent evidence demonstrates that in GBM, microglial-derived EVs contribute to the immune suppression of the tumor microenvironment (TME), thus favoring GBM immune escape. In this review, we report the current knowledge on EV formation, biogenesis, cargo and functions, with a focus on the effects of microglia-derived EVs in GBM. What clearly emerges from this analysis is that we are at the beginning of a full understanding of the complete picture of the biological effects of microglial-derived EVs and that further investigations using multidisciplinary approaches are necessary to validate their use in GBM diagnosis and therapy. more...

Brain homeostasis needs continuous exchange of intercellular information among neurons, glial cells, and immune cells, namely microglial cells. Extracellular vesicles (EVs) are active players of this process. All the cells of the body, including the brain, release at least two subtypes of EVs, the medium/large EVs (m/lEVs) and small EVs (sEVs). sEVs released by microglia play an important role in brain patrolling in physio-pathological processes. One of the most common and malignant forms of brain cancer is glioblastoma. Altered intercellular communications constitute a base for the onset and the development of the disease. In this work, we used microglia-derived sEVs to assay their effects in vitro on murine glioma cells and in vivo in a glioma model on C57BL6/N mice. Our findings indicated that sEVs carry messages to cancer cells that modify glioma cell metabolism, reducing lactate, nitric oxide (NO), and glutamate (Glu) release. sEVs affect Glu homeostasis, increasing the expression of Glu transporter Glt-1 on astrocytes. We demonstrated that these effects are mediated by miR-124 contained in microglia-released sEVs. The in vivo benefit of microglia-derived sEVs results in a significantly reduced tumor mass and an increased survival of glioma-bearing mice, depending on miR-124. more...

Brain homeostasis needs continuous exchange of intercellular information among neurons, glial cells, and immune cells, namely microglial cells. Extracellular vesicles (EVs) are active players of this process. All the cells of the body, including the brain, release at least two subtypes of EVs, the medium/large EVs (m/lEVs) and small EVs (sEVs). sEVs released by microglia play an important role in brain patrolling in physio-pathological processes. One of the most common and malignant forms of brain cancer is glioblastoma. Altered intercellular communications constitute a base for the onset and the development of the disease. In this work, we used microglia-derived sEVs to assay their effects in vitro on murine glioma cells and in vivo in a glioma model on C57BL6/N mice. Our findings indicated that sEVs carry messages to cancer cells that modify glioma cell metabolism, reducing lactate, nitric oxide (NO), and glutamate (Glu) release. sEVs affect Glu homeostasis, increasing the expression of Glu transporter Glt-1 on astrocytes. We demonstrated that these effects are mediated by miR-124 contained in microglia-released sEVs. The in vivo benefit of microglia-derived sEVs results in a significantly reduced tumor mass and an increased survival of glioma-bearing mice, depending on miR-124. more...