Synaptic components are required for glioblastoma progression in Drosophila

Glioblastoma (GB) is the most aggressive, lethal and frequent primary brain tumor. It originates from glial cells and is characterized by rapid expansion through infiltration. GB cells interact with the microenvironment and healthy surrounding tissues, mostly neurons and vessels. GB cells project tu...

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Detalhes bibliográficos
Autores: Losada-Pérez, María, García-Moreno, M.H., García-Ricote, Irene, Casas-Tinto, Sergio
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Recursos:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/284284
Acesso em linha:http://hdl.handle.net/10261/284284
Access Level:acceso abierto
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spelling Synaptic components are required for glioblastoma progression in DrosophilaLosada-Pérez, MaríaGarcía-Moreno, M.H.García-Ricote, IreneCasas-Tinto, SergioGlioblastoma (GB) is the most aggressive, lethal and frequent primary brain tumor. It originates from glial cells and is characterized by rapid expansion through infiltration. GB cells interact with the microenvironment and healthy surrounding tissues, mostly neurons and vessels. GB cells project tumor microtubes (TMs) contact with neurons, and exchange signaling molecules related to Wingless/WNT, JNK, Insulin or Neuroligin-3 pathways. This cell to cell communication promotes GB expansion and neurodegeneration. Moreover, healthy neurons form glutamatergic functional synapses with GB cells which facilitate GB expansion and premature death in mouse GB xerograph models. Targeting signaling and synaptic components of GB progression may become a suitable strategy against glioblastoma. In a Drosophila GB model, we have determined the post-synaptic nature of GB cells with respect to neurons, and the contribution of post-synaptic genes expressed in GB cells to tumor progression. In addition, we document the presence of intratumoral synapses between GB cells, and the functional contribution of pre-synaptic genes to GB calcium dependent activity and expansion. Finally, we explore the relevance of synaptic genes in GB cells to the lifespan reduction caused by GB advance. Our results indicate that both presynaptic and postsynaptic proteins play a role in GB progression and lethality.This research was supported by PID2019-110116GB-100 grant from the Spanish Ministerio de Ciencia e Innovación to S C-T and by a Postdoctoral Fellowship from the Comunidad de Madrid (2016-T2-BMD-1295) to M L-P. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Public Library of ScienceMinisterio de Ciencia e Innovación (España)Comunidad de MadridConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2022202220222022info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/284284reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019-110116GB-I00http://dx.doi.org/10.1371/journal.pgen.1010329Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/2842842026-05-22T06:33:51Z
dc.title.none.fl_str_mv Synaptic components are required for glioblastoma progression in Drosophila
title Synaptic components are required for glioblastoma progression in Drosophila
spellingShingle Synaptic components are required for glioblastoma progression in Drosophila
Losada-Pérez, María
title_short Synaptic components are required for glioblastoma progression in Drosophila
title_full Synaptic components are required for glioblastoma progression in Drosophila
title_fullStr Synaptic components are required for glioblastoma progression in Drosophila
title_full_unstemmed Synaptic components are required for glioblastoma progression in Drosophila
title_sort Synaptic components are required for glioblastoma progression in Drosophila
dc.creator.none.fl_str_mv Losada-Pérez, María
García-Moreno, M.H.
García-Ricote, Irene
Casas-Tinto, Sergio
author Losada-Pérez, María
author_facet Losada-Pérez, María
García-Moreno, M.H.
García-Ricote, Irene
Casas-Tinto, Sergio
author_role author
author2 García-Moreno, M.H.
García-Ricote, Irene
Casas-Tinto, Sergio
author2_role author
author
author
dc.contributor.none.fl_str_mv Ministerio de Ciencia e Innovación (España)
Comunidad de Madrid
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
description Glioblastoma (GB) is the most aggressive, lethal and frequent primary brain tumor. It originates from glial cells and is characterized by rapid expansion through infiltration. GB cells interact with the microenvironment and healthy surrounding tissues, mostly neurons and vessels. GB cells project tumor microtubes (TMs) contact with neurons, and exchange signaling molecules related to Wingless/WNT, JNK, Insulin or Neuroligin-3 pathways. This cell to cell communication promotes GB expansion and neurodegeneration. Moreover, healthy neurons form glutamatergic functional synapses with GB cells which facilitate GB expansion and premature death in mouse GB xerograph models. Targeting signaling and synaptic components of GB progression may become a suitable strategy against glioblastoma. In a Drosophila GB model, we have determined the post-synaptic nature of GB cells with respect to neurons, and the contribution of post-synaptic genes expressed in GB cells to tumor progression. In addition, we document the presence of intratumoral synapses between GB cells, and the functional contribution of pre-synaptic genes to GB calcium dependent activity and expansion. Finally, we explore the relevance of synaptic genes in GB cells to the lifespan reduction caused by GB advance. Our results indicate that both presynaptic and postsynaptic proteins play a role in GB progression and lethality.
publishDate 2022
dc.date.none.fl_str_mv 2022
2022
2022
2022
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/284284
url http://hdl.handle.net/10261/284284
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019-110116GB-I00
http://dx.doi.org/10.1371/journal.pgen.1010329
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Public Library of Science
publisher.none.fl_str_mv Public Library of Science
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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