Crosstalk between glial and glioblastoma cells triggers the "go-or-grow" phenotype of tumor cells
Autor(a) principal: | |
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Data de Publicação: | 2017 |
Outros Autores: | , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10316/108123 https://doi.org/10.1186/s12964-017-0194-x |
Resumo: | 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. |
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Crosstalk between glial and glioblastoma cells triggers the "go-or-grow" phenotype of tumor cellsGlioblastomaGlial cellsTumor microenvironmentSecretomeParacrine effectAnimalsBrain NeoplasmsCell Line, TumorCell SurvivalCells, CulturedCulture Media, ConditionedGlioblastomaMAP Kinase Signaling SystemMiceMice, Inbred C57BLNeurogliaParacrine CommunicationProteomeCell ProliferationPhenotypeBackground: 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.Springer Nature2017-10-02info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://hdl.handle.net/10316/108123http://hdl.handle.net/10316/108123https://doi.org/10.1186/s12964-017-0194-xeng1478-811XOliveira, Ana IsabelAnjo, Sandra I.Vieira de Castro, JoanaSerra, Sofia C.Salgado, António J.Manadas, BrunoCosta, Bruno M.info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-08-11T17:09:20Zoai:estudogeral.uc.pt:10316/108123Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:24:23.390927Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
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 |
spellingShingle |
Crosstalk between glial and glioblastoma cells triggers the "go-or-grow" phenotype of tumor cells Oliveira, Ana Isabel Glioblastoma Glial cells Tumor microenvironment Secretome Paracrine effect Animals Brain Neoplasms Cell Line, Tumor Cell Survival Cells, Cultured Culture Media, Conditioned Glioblastoma MAP Kinase Signaling System Mice Mice, Inbred C57BL Neuroglia Paracrine Communication Proteome Cell Proliferation Phenotype |
title_short |
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_sort |
Crosstalk between glial and glioblastoma cells triggers the "go-or-grow" phenotype of tumor cells |
author |
Oliveira, Ana Isabel |
author_facet |
Oliveira, Ana Isabel Anjo, Sandra I. Vieira de Castro, Joana Serra, Sofia C. Salgado, António J. Manadas, Bruno Costa, Bruno M. |
author_role |
author |
author2 |
Anjo, Sandra I. Vieira de Castro, Joana Serra, Sofia C. Salgado, António J. Manadas, Bruno Costa, Bruno M. |
author2_role |
author author author author author author |
dc.contributor.author.fl_str_mv |
Oliveira, Ana Isabel Anjo, Sandra I. Vieira de Castro, Joana Serra, Sofia C. Salgado, António J. Manadas, Bruno Costa, Bruno M. |
dc.subject.por.fl_str_mv |
Glioblastoma Glial cells Tumor microenvironment Secretome Paracrine effect Animals Brain Neoplasms Cell Line, Tumor Cell Survival Cells, Cultured Culture Media, Conditioned Glioblastoma MAP Kinase Signaling System Mice Mice, Inbred C57BL Neuroglia Paracrine Communication Proteome Cell Proliferation Phenotype |
topic |
Glioblastoma Glial cells Tumor microenvironment Secretome Paracrine effect Animals Brain Neoplasms Cell Line, Tumor Cell Survival Cells, Cultured Culture Media, Conditioned Glioblastoma MAP Kinase Signaling System Mice Mice, Inbred C57BL Neuroglia Paracrine Communication Proteome Cell Proliferation Phenotype |
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. |
publishDate |
2017 |
dc.date.none.fl_str_mv |
2017-10-02 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10316/108123 http://hdl.handle.net/10316/108123 https://doi.org/10.1186/s12964-017-0194-x |
url |
http://hdl.handle.net/10316/108123 https://doi.org/10.1186/s12964-017-0194-x |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
1478-811X |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
Springer Nature |
publisher.none.fl_str_mv |
Springer Nature |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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