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Human Cerebrospinal Fluid Modulates Pathways Promoting Glioblastoma Malignancy
Glioblastoma (GBM) is the most common and devastating primary cancer of the central nervous system in adults. High grade gliomas are able to modify and respond to the brain microenvironment. When GBM tumors infiltrate the Subventricular zone (SVZ) they have a more aggressive clinical presentation th...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7969659/ https://www.ncbi.nlm.nih.gov/pubmed/33747938 http://dx.doi.org/10.3389/fonc.2021.624145 |
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author | Carrano, Anna Zarco, Natanael Phillipps, Jordan Lara-Velazquez, Montserrat Suarez-Meade, Paola Norton, Emily S. Chaichana, Kaisorn L. Quiñones-Hinojosa, Alfredo Asmann, Yan W. Guerrero-Cázares, Hugo |
author_facet | Carrano, Anna Zarco, Natanael Phillipps, Jordan Lara-Velazquez, Montserrat Suarez-Meade, Paola Norton, Emily S. Chaichana, Kaisorn L. Quiñones-Hinojosa, Alfredo Asmann, Yan W. Guerrero-Cázares, Hugo |
author_sort | Carrano, Anna |
collection | PubMed |
description | Glioblastoma (GBM) is the most common and devastating primary cancer of the central nervous system in adults. High grade gliomas are able to modify and respond to the brain microenvironment. When GBM tumors infiltrate the Subventricular zone (SVZ) they have a more aggressive clinical presentation than SVZ-distal tumors. We suggest that cerebrospinal fluid (CSF) contact contributes to enhance GBM malignant characteristics in these tumors. We evaluated the impact of human CSF on GBM, performing a transcriptome analysis on human primary GBM cells exposed to CSF to measure changes in gene expression profile and their clinical relevance on disease outcome. In addition we evaluated the proliferation and migration changes of CSF-exposed GBM cells in vitro and in vivo. CSF induced transcriptomic changes in pathways promoting cell malignancy, such as apoptosis, survival, cell motility, angiogenesis, inflammation, and glucose metabolism. A genetic signature extracted from the identified transcriptional changes in response to CSF proved to be predictive of GBM patient survival using the TCGA database. Furthermore, CSF induced an increase in viability, proliferation rate, and self-renewing capacity, as well as the migratory capabilities of GBM cells in vitro. In vivo, GBM cells co-injected with human CSF generated larger and more proliferative tumors compared to controls. Taken together, these results provide direct evidence that CSF is a key player in determining tumor growth and invasion through the activation of complex gene expression patterns characteristic of a malignant phenotype. These findings have diagnostic and therapeutic implications for GBM patients. The changes induced by CSF contact might play a role in the increased malignancy of SVZ-proximal GBM. |
format | Online Article Text |
id | pubmed-7969659 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-79696592021-03-19 Human Cerebrospinal Fluid Modulates Pathways Promoting Glioblastoma Malignancy Carrano, Anna Zarco, Natanael Phillipps, Jordan Lara-Velazquez, Montserrat Suarez-Meade, Paola Norton, Emily S. Chaichana, Kaisorn L. Quiñones-Hinojosa, Alfredo Asmann, Yan W. Guerrero-Cázares, Hugo Front Oncol Oncology Glioblastoma (GBM) is the most common and devastating primary cancer of the central nervous system in adults. High grade gliomas are able to modify and respond to the brain microenvironment. When GBM tumors infiltrate the Subventricular zone (SVZ) they have a more aggressive clinical presentation than SVZ-distal tumors. We suggest that cerebrospinal fluid (CSF) contact contributes to enhance GBM malignant characteristics in these tumors. We evaluated the impact of human CSF on GBM, performing a transcriptome analysis on human primary GBM cells exposed to CSF to measure changes in gene expression profile and their clinical relevance on disease outcome. In addition we evaluated the proliferation and migration changes of CSF-exposed GBM cells in vitro and in vivo. CSF induced transcriptomic changes in pathways promoting cell malignancy, such as apoptosis, survival, cell motility, angiogenesis, inflammation, and glucose metabolism. A genetic signature extracted from the identified transcriptional changes in response to CSF proved to be predictive of GBM patient survival using the TCGA database. Furthermore, CSF induced an increase in viability, proliferation rate, and self-renewing capacity, as well as the migratory capabilities of GBM cells in vitro. In vivo, GBM cells co-injected with human CSF generated larger and more proliferative tumors compared to controls. Taken together, these results provide direct evidence that CSF is a key player in determining tumor growth and invasion through the activation of complex gene expression patterns characteristic of a malignant phenotype. These findings have diagnostic and therapeutic implications for GBM patients. The changes induced by CSF contact might play a role in the increased malignancy of SVZ-proximal GBM. Frontiers Media S.A. 2021-03-04 /pmc/articles/PMC7969659/ /pubmed/33747938 http://dx.doi.org/10.3389/fonc.2021.624145 Text en Copyright © 2021 Carrano, Zarco, Phillipps, Lara-Velazquez, Suarez-Meade, Norton, Chaichana, Quiñones-Hinojosa, Asmann and Guerrero-Cázares. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Oncology Carrano, Anna Zarco, Natanael Phillipps, Jordan Lara-Velazquez, Montserrat Suarez-Meade, Paola Norton, Emily S. Chaichana, Kaisorn L. Quiñones-Hinojosa, Alfredo Asmann, Yan W. Guerrero-Cázares, Hugo Human Cerebrospinal Fluid Modulates Pathways Promoting Glioblastoma Malignancy |
title | Human Cerebrospinal Fluid Modulates Pathways Promoting Glioblastoma Malignancy |
title_full | Human Cerebrospinal Fluid Modulates Pathways Promoting Glioblastoma Malignancy |
title_fullStr | Human Cerebrospinal Fluid Modulates Pathways Promoting Glioblastoma Malignancy |
title_full_unstemmed | Human Cerebrospinal Fluid Modulates Pathways Promoting Glioblastoma Malignancy |
title_short | Human Cerebrospinal Fluid Modulates Pathways Promoting Glioblastoma Malignancy |
title_sort | human cerebrospinal fluid modulates pathways promoting glioblastoma malignancy |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7969659/ https://www.ncbi.nlm.nih.gov/pubmed/33747938 http://dx.doi.org/10.3389/fonc.2021.624145 |
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