Glioblastoma hijacks microglial gene expression to support tumor growth
Abstract Background Glioblastomas are the most common and lethal primary brain tumors. Microglia, the resident immune cells of the brain, survey their environment and respond to pathogens, toxins, and tumors. Glioblastoma cells communicate with microglia, in part by releasing extracellular vesicles...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2020-04-01
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| Series: | Journal of Neuroinflammation |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12974-020-01797-2 |
| _version_ | 1818290922719281152 |
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| author | Sybren L. N. Maas Erik R. Abels Lieke L. Van De Haar Xuan Zhang Liza Morsett Srinjoy Sil Joana Guedes Pritha Sen Shilpa Prabhakar Suzanne E. Hickman Charles P. Lai David T. Ting Xandra O. Breakefield Marike L. D. Broekman Joseph El Khoury |
| author_facet | Sybren L. N. Maas Erik R. Abels Lieke L. Van De Haar Xuan Zhang Liza Morsett Srinjoy Sil Joana Guedes Pritha Sen Shilpa Prabhakar Suzanne E. Hickman Charles P. Lai David T. Ting Xandra O. Breakefield Marike L. D. Broekman Joseph El Khoury |
| author_sort | Sybren L. N. Maas |
| collection | DOAJ |
| description | Abstract Background Glioblastomas are the most common and lethal primary brain tumors. Microglia, the resident immune cells of the brain, survey their environment and respond to pathogens, toxins, and tumors. Glioblastoma cells communicate with microglia, in part by releasing extracellular vesicles (EVs). Despite the presence of large numbers of microglia in glioblastoma, the tumors continue to grow, and these neuroimmune cells appear incapable of keeping the tumor in check. To understand this process, we analyzed gene expression in microglia interacting with glioblastoma cells. Methods We used RNASeq of isolated microglia to analyze the expression patterns of genes involved in key microglial functions in mice with glioblastoma. We focused on microglia that had taken up tumor-derived EVs and therefore were within and immediately adjacent to the tumor. Results We show that these microglia have downregulated expression of genes involved in sensing tumor cells and tumor-derived danger signals, as well as genes used for tumor killing. In contrast, expression of genes involved in facilitating tumor spread was upregulated. These changes appear to be in part EV-mediated, since intracranial injection of EVs in normal mice led to similar transcriptional changes in microglia. We observed a similar microglial transcriptomic signature when we analyzed datasets from human patients with glioblastoma. Conclusion Our data define a microgliaGlioblastoma specific phenotype, whereby glioblastomas have hijacked gene expression in the neuroimmune system to favor avoiding tumor sensing, suppressing the immune response, clearing a path for invasion, and enhancing tumor propagation. For further exploration, we developed an interactive online tool at http://www.glioma-microglia.com with all expression data and additional functional and pathway information for each gene. |
| first_indexed | 2024-12-13T02:35:52Z |
| format | Article |
| id | doaj.art-b9621698f61b420098d1d9686658007c |
| institution | Directory Open Access Journal |
| issn | 1742-2094 |
| language | English |
| last_indexed | 2024-12-13T02:35:52Z |
| publishDate | 2020-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Neuroinflammation |
| spelling | doaj.art-b9621698f61b420098d1d9686658007c2022-12-22T00:02:25ZengBMCJournal of Neuroinflammation1742-20942020-04-0117111810.1186/s12974-020-01797-2Glioblastoma hijacks microglial gene expression to support tumor growthSybren L. N. Maas0Erik R. Abels1Lieke L. Van De Haar2Xuan Zhang3Liza Morsett4Srinjoy Sil5Joana Guedes6Pritha Sen7Shilpa Prabhakar8Suzanne E. Hickman9Charles P. Lai10David T. Ting11Xandra O. Breakefield12Marike L. D. Broekman13Joseph El Khoury14Departments of Neurology and Radiology, Massachusetts General Hospital, Harvard Medical SchoolDepartments of Neurology and Radiology, Massachusetts General Hospital, Harvard Medical SchoolDepartments of Neurology and Radiology, Massachusetts General Hospital, Harvard Medical SchoolDepartments of Neurology and Radiology, Massachusetts General Hospital, Harvard Medical SchoolCenter for Immunology & Inflammatory Diseases, Massachusetts General Hospital, Harvard Medical SchoolCancer Center, Massachusetts General Hospital, Harvard Medical SchoolCenter for Immunology & Inflammatory Diseases, Massachusetts General Hospital, Harvard Medical SchoolCenter for Immunology & Inflammatory Diseases, Massachusetts General Hospital, Harvard Medical SchoolDepartments of Neurology and Radiology, Massachusetts General Hospital, Harvard Medical SchoolCenter for Immunology & Inflammatory Diseases, Massachusetts General Hospital, Harvard Medical SchoolDepartments of Neurology and Radiology, Massachusetts General Hospital, Harvard Medical SchoolCancer Center, Massachusetts General Hospital, Harvard Medical SchoolDepartments of Neurology and Radiology, Massachusetts General Hospital, Harvard Medical SchoolDepartments of Neurology and Radiology, Massachusetts General Hospital, Harvard Medical SchoolCenter for Immunology & Inflammatory Diseases, Massachusetts General Hospital, Harvard Medical SchoolAbstract Background Glioblastomas are the most common and lethal primary brain tumors. Microglia, the resident immune cells of the brain, survey their environment and respond to pathogens, toxins, and tumors. Glioblastoma cells communicate with microglia, in part by releasing extracellular vesicles (EVs). Despite the presence of large numbers of microglia in glioblastoma, the tumors continue to grow, and these neuroimmune cells appear incapable of keeping the tumor in check. To understand this process, we analyzed gene expression in microglia interacting with glioblastoma cells. Methods We used RNASeq of isolated microglia to analyze the expression patterns of genes involved in key microglial functions in mice with glioblastoma. We focused on microglia that had taken up tumor-derived EVs and therefore were within and immediately adjacent to the tumor. Results We show that these microglia have downregulated expression of genes involved in sensing tumor cells and tumor-derived danger signals, as well as genes used for tumor killing. In contrast, expression of genes involved in facilitating tumor spread was upregulated. These changes appear to be in part EV-mediated, since intracranial injection of EVs in normal mice led to similar transcriptional changes in microglia. We observed a similar microglial transcriptomic signature when we analyzed datasets from human patients with glioblastoma. Conclusion Our data define a microgliaGlioblastoma specific phenotype, whereby glioblastomas have hijacked gene expression in the neuroimmune system to favor avoiding tumor sensing, suppressing the immune response, clearing a path for invasion, and enhancing tumor propagation. For further exploration, we developed an interactive online tool at http://www.glioma-microglia.com with all expression data and additional functional and pathway information for each gene.http://link.springer.com/article/10.1186/s12974-020-01797-2GlioblastomaGliomaMicrogliaExtracellular vesiclesExosomesMicrovesicles |
| spellingShingle | Sybren L. N. Maas Erik R. Abels Lieke L. Van De Haar Xuan Zhang Liza Morsett Srinjoy Sil Joana Guedes Pritha Sen Shilpa Prabhakar Suzanne E. Hickman Charles P. Lai David T. Ting Xandra O. Breakefield Marike L. D. Broekman Joseph El Khoury Glioblastoma hijacks microglial gene expression to support tumor growth Journal of Neuroinflammation Glioblastoma Glioma Microglia Extracellular vesicles Exosomes Microvesicles |
| title | Glioblastoma hijacks microglial gene expression to support tumor growth |
| title_full | Glioblastoma hijacks microglial gene expression to support tumor growth |
| title_fullStr | Glioblastoma hijacks microglial gene expression to support tumor growth |
| title_full_unstemmed | Glioblastoma hijacks microglial gene expression to support tumor growth |
| title_short | Glioblastoma hijacks microglial gene expression to support tumor growth |
| title_sort | glioblastoma hijacks microglial gene expression to support tumor growth |
| topic | Glioblastoma Glioma Microglia Extracellular vesicles Exosomes Microvesicles |
| url | http://link.springer.com/article/10.1186/s12974-020-01797-2 |
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