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.

Microglia-Derived Small Extracellular Vesicles Reduce Glioma Growth by Modifying Tumor Cell Metabolism and Enhancing Glutamate Clearance through miR-124 / Serpe, Carmela; Monaco, Lucia; Relucenti, Michela; Iovino, Ludovica; Familiari, Pietro; Scavizzi, Ferdinando; Raspa, Marcello; Familiari, Giuseppe; Civiero, Laura; D'Agnano, Igea; Limatola, Cristina; Catalano, Myriam. - In: CELLS. - ISSN 2073-4409. - 10:8(2021), p. 2066. [10.3390/cells10082066]

Microglia-Derived Small Extracellular Vesicles Reduce Glioma Growth by Modifying Tumor Cell Metabolism and Enhancing Glutamate Clearance through miR-124

Serpe, Carmela;Monaco, Lucia;Relucenti, Michela;Familiari, Pietro;Raspa, Marcello;Familiari, Giuseppe;Limatola, Cristina;Catalano, Myriam
2021

Abstract

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.
2021
Glt-1; brain tumors; extracellular vesicles; glioma; glutamate; miR-124; microglia; neurotoxicity
01 Pubblicazione su rivista::01a Articolo in rivista
Microglia-Derived Small Extracellular Vesicles Reduce Glioma Growth by Modifying Tumor Cell Metabolism and Enhancing Glutamate Clearance through miR-124 / Serpe, Carmela; Monaco, Lucia; Relucenti, Michela; Iovino, Ludovica; Familiari, Pietro; Scavizzi, Ferdinando; Raspa, Marcello; Familiari, Giuseppe; Civiero, Laura; D'Agnano, Igea; Limatola, Cristina; Catalano, Myriam. - In: CELLS. - ISSN 2073-4409. - 10:8(2021), p. 2066. [10.3390/cells10082066]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1568283
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