A heterotypic tridimensional model to study the interaction of macrophages and glioblastoma in vitro

Autores
Gattas, María José; Estecho, Ivana Gisele; Lago Huvelle, María Amparo; Errasti, Andrea Emilse; Carrera Silva, Eugenio Antonio; Simian, Marina
Año de publicación
2021
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Background: Glioblastoma multiforme (GBM) is the most frequent and aggressive primary brain tumor, and macrophages account for 30–40% of its composition. Most of these macrophages derive from bone marrow monocytes playing a crucial role in tumor progression. Unraveling the mechanisms of macrophages-GBM crosstalk in an appropriate model will contribute to the development of specific and more successful therapies. We investigated the interaction of U87MG human GBM cells with primary human CD14+ monocytes or the THP-1 cell line with the aim of establishing a physiologically relevant heterotypic culture model. Methods: primary monocytes and THP-1 cells were cultured in the presence of U87MG conditioned media or co-cultured together with previously formed GBM spheroids. Monocyte differentiation was determined by flow cytometry. Results: primary monocytes differentiate to M2 macrophages when incubated with U87MG conditioned media in 2-dimensional culture, as determined by the increased percentage of CD14+CD206+ and CD64+CD206+ populations in CD11b+ cells. Moreover, the mitochondrial protein p32/gC1qR is expressed in monocytes exposed to U87MG conditioned media. When primary CD14+ monocytes or THP-1 cells are added to previously formed GBM spheroids, both invade and establish within them. However, only primary monocytes differentiate and acquire a clear M2 phenotype characterized by the upregulation of CD206, CD163, and MERTK surface markers on the CD11b+CD14+ population and induce alterations in the sphericity of the cell cultures. Conclusion: our results present a new physiologically relevant model to study GBM/macrophage interactions in a human setting and suggest that both soluble GBM factors, as well as cell-contact dependent signals, are strong inducers of anti-inflammatory macrophages within the tumor niche.
Fil: Gattas, María José. Universidad Nacional de San Martin. Instituto de Nanosistemas; Argentina
Fil: Estecho, Ivana Gisele. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Farmacología; Argentina
Fil: Lago Huvelle, María Amparo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de San Martin. Instituto de Nanosistemas; Argentina
Fil: Errasti, Andrea Emilse. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Farmacología; Argentina. Instituto Superior de Formacion Docente y Tecnica Numero 24 Doctor Bernardo Houssay.; Argentina
Fil: Carrera Silva, Eugenio Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Simian, Marina. Universidad Nacional de San Martin. Instituto de Nanosistemas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Materia
3D CULTURES
CD206
GLIOBLASTOMA MULTIFORME
MACROPHAGE POLARIZATION
MONOCYTES
TUMOR-STROMAL INTERACTIONS
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/148353
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/148353
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling A heterotypic tridimensional model to study the interaction of macrophages and glioblastoma in vitroGattas, María JoséEstecho, Ivana GiseleLago Huvelle, María AmparoErrasti, Andrea EmilseCarrera Silva, Eugenio AntonioSimian, Marina3D CULTURESCD206GLIOBLASTOMA MULTIFORMEMACROPHAGE POLARIZATIONMONOCYTESTUMOR-STROMAL INTERACTIONShttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Background: Glioblastoma multiforme (GBM) is the most frequent and aggressive primary brain tumor, and macrophages account for 30–40% of its composition. Most of these macrophages derive from bone marrow monocytes playing a crucial role in tumor progression. Unraveling the mechanisms of macrophages-GBM crosstalk in an appropriate model will contribute to the development of specific and more successful therapies. We investigated the interaction of U87MG human GBM cells with primary human CD14+ monocytes or the THP-1 cell line with the aim of establishing a physiologically relevant heterotypic culture model. Methods: primary monocytes and THP-1 cells were cultured in the presence of U87MG conditioned media or co-cultured together with previously formed GBM spheroids. Monocyte differentiation was determined by flow cytometry. Results: primary monocytes differentiate to M2 macrophages when incubated with U87MG conditioned media in 2-dimensional culture, as determined by the increased percentage of CD14+CD206+ and CD64+CD206+ populations in CD11b+ cells. Moreover, the mitochondrial protein p32/gC1qR is expressed in monocytes exposed to U87MG conditioned media. When primary CD14+ monocytes or THP-1 cells are added to previously formed GBM spheroids, both invade and establish within them. However, only primary monocytes differentiate and acquire a clear M2 phenotype characterized by the upregulation of CD206, CD163, and MERTK surface markers on the CD11b+CD14+ population and induce alterations in the sphericity of the cell cultures. Conclusion: our results present a new physiologically relevant model to study GBM/macrophage interactions in a human setting and suggest that both soluble GBM factors, as well as cell-contact dependent signals, are strong inducers of anti-inflammatory macrophages within the tumor niche.Fil: Gattas, María José. Universidad Nacional de San Martin. Instituto de Nanosistemas; ArgentinaFil: Estecho, Ivana Gisele. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Farmacología; ArgentinaFil: Lago Huvelle, María Amparo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de San Martin. Instituto de Nanosistemas; ArgentinaFil: Errasti, Andrea Emilse. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Farmacología; Argentina. Instituto Superior de Formacion Docente y Tecnica Numero 24 Doctor Bernardo Houssay.; ArgentinaFil: Carrera Silva, Eugenio Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Simian, Marina. Universidad Nacional de San Martin. Instituto de Nanosistemas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaMolecular Diversity Preservation International2021-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/148353Gattas, María José; Estecho, Ivana Gisele; Lago Huvelle, María Amparo; Errasti, Andrea Emilse; Carrera Silva, Eugenio Antonio; et al.; A heterotypic tridimensional model to study the interaction of macrophages and glioblastoma in vitro; Molecular Diversity Preservation International; International Journal of Molecular Sciences; 22; 10; 5-2021; 1-151422-0067CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.3390/ijms22105105info:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/1422-0067/22/10/5105info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:58:12Zoai:ri.conicet.gov.ar:11336/148353instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 09:58:12.937CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv A heterotypic tridimensional model to study the interaction of macrophages and glioblastoma in vitro
title A heterotypic tridimensional model to study the interaction of macrophages and glioblastoma in vitro
spellingShingle A heterotypic tridimensional model to study the interaction of macrophages and glioblastoma in vitro
Gattas, María José
3D CULTURES
CD206
GLIOBLASTOMA MULTIFORME
MACROPHAGE POLARIZATION
MONOCYTES
TUMOR-STROMAL INTERACTIONS
title_short A heterotypic tridimensional model to study the interaction of macrophages and glioblastoma in vitro
title_full A heterotypic tridimensional model to study the interaction of macrophages and glioblastoma in vitro
title_fullStr A heterotypic tridimensional model to study the interaction of macrophages and glioblastoma in vitro
title_full_unstemmed A heterotypic tridimensional model to study the interaction of macrophages and glioblastoma in vitro
title_sort A heterotypic tridimensional model to study the interaction of macrophages and glioblastoma in vitro
dc.creator.none.fl_str_mv Gattas, María José
Estecho, Ivana Gisele
Lago Huvelle, María Amparo
Errasti, Andrea Emilse
Carrera Silva, Eugenio Antonio
Simian, Marina
author Gattas, María José
author_facet Gattas, María José
Estecho, Ivana Gisele
Lago Huvelle, María Amparo
Errasti, Andrea Emilse
Carrera Silva, Eugenio Antonio
Simian, Marina
author_role author
author2 Estecho, Ivana Gisele
Lago Huvelle, María Amparo
Errasti, Andrea Emilse
Carrera Silva, Eugenio Antonio
Simian, Marina
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv 3D CULTURES
CD206
GLIOBLASTOMA MULTIFORME
MACROPHAGE POLARIZATION
MONOCYTES
TUMOR-STROMAL INTERACTIONS
topic 3D CULTURES
CD206
GLIOBLASTOMA MULTIFORME
MACROPHAGE POLARIZATION
MONOCYTES
TUMOR-STROMAL INTERACTIONS
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Background: Glioblastoma multiforme (GBM) is the most frequent and aggressive primary brain tumor, and macrophages account for 30–40% of its composition. Most of these macrophages derive from bone marrow monocytes playing a crucial role in tumor progression. Unraveling the mechanisms of macrophages-GBM crosstalk in an appropriate model will contribute to the development of specific and more successful therapies. We investigated the interaction of U87MG human GBM cells with primary human CD14+ monocytes or the THP-1 cell line with the aim of establishing a physiologically relevant heterotypic culture model. Methods: primary monocytes and THP-1 cells were cultured in the presence of U87MG conditioned media or co-cultured together with previously formed GBM spheroids. Monocyte differentiation was determined by flow cytometry. Results: primary monocytes differentiate to M2 macrophages when incubated with U87MG conditioned media in 2-dimensional culture, as determined by the increased percentage of CD14+CD206+ and CD64+CD206+ populations in CD11b+ cells. Moreover, the mitochondrial protein p32/gC1qR is expressed in monocytes exposed to U87MG conditioned media. When primary CD14+ monocytes or THP-1 cells are added to previously formed GBM spheroids, both invade and establish within them. However, only primary monocytes differentiate and acquire a clear M2 phenotype characterized by the upregulation of CD206, CD163, and MERTK surface markers on the CD11b+CD14+ population and induce alterations in the sphericity of the cell cultures. Conclusion: our results present a new physiologically relevant model to study GBM/macrophage interactions in a human setting and suggest that both soluble GBM factors, as well as cell-contact dependent signals, are strong inducers of anti-inflammatory macrophages within the tumor niche.
Fil: Gattas, María José. Universidad Nacional de San Martin. Instituto de Nanosistemas; Argentina
Fil: Estecho, Ivana Gisele. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Farmacología; Argentina
Fil: Lago Huvelle, María Amparo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de San Martin. Instituto de Nanosistemas; Argentina
Fil: Errasti, Andrea Emilse. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Farmacología; Argentina. Instituto Superior de Formacion Docente y Tecnica Numero 24 Doctor Bernardo Houssay.; Argentina
Fil: Carrera Silva, Eugenio Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Simian, Marina. Universidad Nacional de San Martin. Instituto de Nanosistemas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
description Background: Glioblastoma multiforme (GBM) is the most frequent and aggressive primary brain tumor, and macrophages account for 30–40% of its composition. Most of these macrophages derive from bone marrow monocytes playing a crucial role in tumor progression. Unraveling the mechanisms of macrophages-GBM crosstalk in an appropriate model will contribute to the development of specific and more successful therapies. We investigated the interaction of U87MG human GBM cells with primary human CD14+ monocytes or the THP-1 cell line with the aim of establishing a physiologically relevant heterotypic culture model. Methods: primary monocytes and THP-1 cells were cultured in the presence of U87MG conditioned media or co-cultured together with previously formed GBM spheroids. Monocyte differentiation was determined by flow cytometry. Results: primary monocytes differentiate to M2 macrophages when incubated with U87MG conditioned media in 2-dimensional culture, as determined by the increased percentage of CD14+CD206+ and CD64+CD206+ populations in CD11b+ cells. Moreover, the mitochondrial protein p32/gC1qR is expressed in monocytes exposed to U87MG conditioned media. When primary CD14+ monocytes or THP-1 cells are added to previously formed GBM spheroids, both invade and establish within them. However, only primary monocytes differentiate and acquire a clear M2 phenotype characterized by the upregulation of CD206, CD163, and MERTK surface markers on the CD11b+CD14+ population and induce alterations in the sphericity of the cell cultures. Conclusion: our results present a new physiologically relevant model to study GBM/macrophage interactions in a human setting and suggest that both soluble GBM factors, as well as cell-contact dependent signals, are strong inducers of anti-inflammatory macrophages within the tumor niche.
publishDate 2021
dc.date.none.fl_str_mv 2021-05
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/148353
Gattas, María José; Estecho, Ivana Gisele; Lago Huvelle, María Amparo; Errasti, Andrea Emilse; Carrera Silva, Eugenio Antonio; et al.; A heterotypic tridimensional model to study the interaction of macrophages and glioblastoma in vitro; Molecular Diversity Preservation International; International Journal of Molecular Sciences; 22; 10; 5-2021; 1-15
1422-0067
CONICET Digital
CONICET
url http://hdl.handle.net/11336/148353
identifier_str_mv Gattas, María José; Estecho, Ivana Gisele; Lago Huvelle, María Amparo; Errasti, Andrea Emilse; Carrera Silva, Eugenio Antonio; et al.; A heterotypic tridimensional model to study the interaction of macrophages and glioblastoma in vitro; Molecular Diversity Preservation International; International Journal of Molecular Sciences; 22; 10; 5-2021; 1-15
1422-0067
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.3390/ijms22105105
info:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/1422-0067/22/10/5105
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Molecular Diversity Preservation International
publisher.none.fl_str_mv Molecular Diversity Preservation International
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.13397

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