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Crosstalk between glial and glioblastoma cells triggers the “go-or-grow” phenotype of tumor cells

BACKGROUND: Glioblastoma (GBM), the most malignant primary brain tumor, leads to poor and unpredictable clinical outcomes. Recent studies showed the tumor microenvironment has a critical role in regulating tumor growth by establishing a complex network of interactions with tumor cells. In this conte...

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Autores principales: Oliveira, Ana Isabel, Anjo, Sandra I., Vieira de Castro, Joana, Serra, Sofia C., Salgado, António J., Manadas, Bruno, Costa, Bruno M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5625790/
https://www.ncbi.nlm.nih.gov/pubmed/28969644
http://dx.doi.org/10.1186/s12964-017-0194-x
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author Oliveira, Ana Isabel
Anjo, Sandra I.
Vieira de Castro, Joana
Serra, Sofia C.
Salgado, António J.
Manadas, Bruno
Costa, Bruno M.
author_facet Oliveira, Ana Isabel
Anjo, Sandra I.
Vieira de Castro, Joana
Serra, Sofia C.
Salgado, António J.
Manadas, Bruno
Costa, Bruno M.
author_sort Oliveira, Ana Isabel
collection PubMed
description BACKGROUND: Glioblastoma (GBM), the most malignant primary brain tumor, leads to poor and unpredictable clinical outcomes. Recent studies showed the tumor microenvironment has a critical role in regulating tumor growth by establishing a complex network of interactions with tumor cells. In this context, we investigated how GBM cells modulate resident glial cells, particularly their paracrine activity, and how this modulation can influence back on the malignant phenotype of GBM cells. METHODS: Conditioned media (CM) of primary mouse glial cultures unexposed (unprimed) or exposed (primed) to the secretome of GL261 GBM cells were analyzed by proteomic analysis. Additionally, these CM were used in GBM cells to evaluate their impact in glioma cell viability, migration capacity and activation of tumor-related intracellular pathways. RESULTS: The proteomic analysis revealed that the pre-exposure of glial cells to CM from GBM cells led to the upregulation of several proteins related to inflammatory response, cell adhesion and extracellular structure organization within the secretome of primed glial cells. At the functional levels, CM derived from unprimed glial cells favored an increase in GBM cell migration capacity, while CM from primed glial cells promoted cells viability. These effects on GBM cells were accompanied by activation of particular intracellular cancer-related pathways, mainly the MAPK/ERK pathway, which is a known regulator of cell proliferation. CONCLUSIONS: Together, our results suggest that glial cells can impact on the pathophysiology of GBM tumors, and that the secretome of GBM cells is able to modulate the secretome of neighboring glial cells, in a way that regulates the “go-or-grow” phenotypic switch of GBM cells. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12964-017-0194-x) contains supplementary material, which is available to authorized users.
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spelling pubmed-56257902017-10-12 Crosstalk between glial and glioblastoma cells triggers the “go-or-grow” phenotype of tumor cells Oliveira, Ana Isabel Anjo, Sandra I. Vieira de Castro, Joana Serra, Sofia C. Salgado, António J. Manadas, Bruno Costa, Bruno M. Cell Commun Signal Research BACKGROUND: Glioblastoma (GBM), the most malignant primary brain tumor, leads to poor and unpredictable clinical outcomes. Recent studies showed the tumor microenvironment has a critical role in regulating tumor growth by establishing a complex network of interactions with tumor cells. In this context, we investigated how GBM cells modulate resident glial cells, particularly their paracrine activity, and how this modulation can influence back on the malignant phenotype of GBM cells. METHODS: Conditioned media (CM) of primary mouse glial cultures unexposed (unprimed) or exposed (primed) to the secretome of GL261 GBM cells were analyzed by proteomic analysis. Additionally, these CM were used in GBM cells to evaluate their impact in glioma cell viability, migration capacity and activation of tumor-related intracellular pathways. RESULTS: The proteomic analysis revealed that the pre-exposure of glial cells to CM from GBM cells led to the upregulation of several proteins related to inflammatory response, cell adhesion and extracellular structure organization within the secretome of primed glial cells. At the functional levels, CM derived from unprimed glial cells favored an increase in GBM cell migration capacity, while CM from primed glial cells promoted cells viability. These effects on GBM cells were accompanied by activation of particular intracellular cancer-related pathways, mainly the MAPK/ERK pathway, which is a known regulator of cell proliferation. CONCLUSIONS: Together, our results suggest that glial cells can impact on the pathophysiology of GBM tumors, and that the secretome of GBM cells is able to modulate the secretome of neighboring glial cells, in a way that regulates the “go-or-grow” phenotypic switch of GBM cells. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12964-017-0194-x) contains supplementary material, which is available to authorized users. BioMed Central 2017-10-02 /pmc/articles/PMC5625790/ /pubmed/28969644 http://dx.doi.org/10.1186/s12964-017-0194-x Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Oliveira, Ana Isabel
Anjo, Sandra I.
Vieira de Castro, Joana
Serra, Sofia C.
Salgado, António J.
Manadas, Bruno
Costa, Bruno M.
Crosstalk between glial and glioblastoma cells triggers the “go-or-grow” phenotype of tumor cells
title Crosstalk between glial and glioblastoma cells triggers the “go-or-grow” phenotype of tumor cells
title_full Crosstalk between glial and glioblastoma cells triggers the “go-or-grow” phenotype of tumor cells
title_fullStr Crosstalk between glial and glioblastoma cells triggers the “go-or-grow” phenotype of tumor cells
title_full_unstemmed Crosstalk between glial and glioblastoma cells triggers the “go-or-grow” phenotype of tumor cells
title_short Crosstalk between glial and glioblastoma cells triggers the “go-or-grow” phenotype of tumor cells
title_sort crosstalk between glial and glioblastoma cells triggers the “go-or-grow” phenotype of tumor cells
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5625790/
https://www.ncbi.nlm.nih.gov/pubmed/28969644
http://dx.doi.org/10.1186/s12964-017-0194-x
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