Microglia-Derived Small Extracellular Vesicles Reduce Glioma Growth by Modifying Tumor Cell Metabolism and Enhancing Glutamate Clearance through miR-124
Autor: | Lucia Monaco, Giuseppe Familiari, Igea D'Agnano, Pietro Familiari, Ferdinando Scavizzi, Michela Relucenti, Laura Civiero, Myriam Catalano, Ludovica Iovino, Carmela Serpe, Marcello Raspa, Cristina Limatola |
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Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
Lipopolysaccharides
Male Glt-1 QH301-705.5 Glutamic Acid microglia glutamate Kaplan-Meier Estimate Nitric Oxide Article brain tumors extracellular vesicles glioma miR-124 neurotoxicity Interferon-gamma Mice In vivo Glioma medicine Animals Biology (General) Cells Cultured Cell Proliferation Microglia Chemistry Brain Neoplasms Glutamate receptor Neurotoxicity Antagomirs General Medicine respiratory system medicine.disease Cell biology Up-Regulation Mice Inbred C57BL MicroRNAs medicine.anatomical_structure Excitatory Amino Acid Transporter 2 Cancer cell Intracellular Homeostasis |
Zdroj: | Cells, Vol 10, Iss 2066, p 2066 (2021) Cells Volume 10 Issue 8 |
Popis: | 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. |
Databáze: | OpenAIRE |
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