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Tumor Microenvironment and Immune Escape in the Time Course of Glioblastoma
Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor with a malignant prognosis. GBM is characterized by high cellular heterogeneity and its progression relies on the interaction with the central nervous system, which ensures the immune-escape and tumor promotion. This interplay...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Springer US
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9525332/ https://www.ncbi.nlm.nih.gov/pubmed/36048342 http://dx.doi.org/10.1007/s12035-022-02996-z |
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author | Virtuoso, Assunta De Luca, Ciro Cirillo, Giovanni Riva, Matteo Romano, Gabriele Bentivegna, Angela Lavitrano, Marialuisa Papa, Michele Giovannoni, Roberto |
author_facet | Virtuoso, Assunta De Luca, Ciro Cirillo, Giovanni Riva, Matteo Romano, Gabriele Bentivegna, Angela Lavitrano, Marialuisa Papa, Michele Giovannoni, Roberto |
author_sort | Virtuoso, Assunta |
collection | PubMed |
description | Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor with a malignant prognosis. GBM is characterized by high cellular heterogeneity and its progression relies on the interaction with the central nervous system, which ensures the immune-escape and tumor promotion. This interplay induces metabolic, (epi)-genetic and molecular rewiring in both domains. In the present study, we aim to characterize the time-related changes in the GBM landscape, using a syngeneic mouse model of primary GBM. GL261 glioma cells were injected in the right striatum of immuno-competent C57Bl/6 mice and animals were sacrificed after 7, 14, and 21 days (7D, 14D, 21D). The tumor development was assessed through 3D tomographic imaging and brains were processed for immunohistochemistry, immunofluorescence, and western blotting. A human transcriptomic database was inquired to support the translational value of the experimental data. Our results showed the dynamic of the tumor progression, being established as a bulk at 14D and surrounded by a dense scar of reactive astrocytes. The GBM growth was paralleled by the impairment in the microglial/macrophagic recruitment and antigen-presenting functions, while the invasive phase was characterized by changes in the extracellular matrix, as shown by the analysis of tenascin C and metalloproteinase-9. The present study emphasizes the role of the molecular changes in the microenvironment during the GBM progression, fostering the development of novel multi-targeted, time-dependent therapies in an experimental model similar to the human disease. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12035-022-02996-z. |
format | Online Article Text |
id | pubmed-9525332 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Springer US |
record_format | MEDLINE/PubMed |
spelling | pubmed-95253322022-10-02 Tumor Microenvironment and Immune Escape in the Time Course of Glioblastoma Virtuoso, Assunta De Luca, Ciro Cirillo, Giovanni Riva, Matteo Romano, Gabriele Bentivegna, Angela Lavitrano, Marialuisa Papa, Michele Giovannoni, Roberto Mol Neurobiol Article Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor with a malignant prognosis. GBM is characterized by high cellular heterogeneity and its progression relies on the interaction with the central nervous system, which ensures the immune-escape and tumor promotion. This interplay induces metabolic, (epi)-genetic and molecular rewiring in both domains. In the present study, we aim to characterize the time-related changes in the GBM landscape, using a syngeneic mouse model of primary GBM. GL261 glioma cells were injected in the right striatum of immuno-competent C57Bl/6 mice and animals were sacrificed after 7, 14, and 21 days (7D, 14D, 21D). The tumor development was assessed through 3D tomographic imaging and brains were processed for immunohistochemistry, immunofluorescence, and western blotting. A human transcriptomic database was inquired to support the translational value of the experimental data. Our results showed the dynamic of the tumor progression, being established as a bulk at 14D and surrounded by a dense scar of reactive astrocytes. The GBM growth was paralleled by the impairment in the microglial/macrophagic recruitment and antigen-presenting functions, while the invasive phase was characterized by changes in the extracellular matrix, as shown by the analysis of tenascin C and metalloproteinase-9. The present study emphasizes the role of the molecular changes in the microenvironment during the GBM progression, fostering the development of novel multi-targeted, time-dependent therapies in an experimental model similar to the human disease. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12035-022-02996-z. Springer US 2022-09-01 2022 /pmc/articles/PMC9525332/ /pubmed/36048342 http://dx.doi.org/10.1007/s12035-022-02996-z Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Virtuoso, Assunta De Luca, Ciro Cirillo, Giovanni Riva, Matteo Romano, Gabriele Bentivegna, Angela Lavitrano, Marialuisa Papa, Michele Giovannoni, Roberto Tumor Microenvironment and Immune Escape in the Time Course of Glioblastoma |
title | Tumor Microenvironment and Immune Escape in the Time Course of Glioblastoma |
title_full | Tumor Microenvironment and Immune Escape in the Time Course of Glioblastoma |
title_fullStr | Tumor Microenvironment and Immune Escape in the Time Course of Glioblastoma |
title_full_unstemmed | Tumor Microenvironment and Immune Escape in the Time Course of Glioblastoma |
title_short | Tumor Microenvironment and Immune Escape in the Time Course of Glioblastoma |
title_sort | tumor microenvironment and immune escape in the time course of glioblastoma |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9525332/ https://www.ncbi.nlm.nih.gov/pubmed/36048342 http://dx.doi.org/10.1007/s12035-022-02996-z |
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