Connexin43 peptide, TAT-Cx43266–283, selectively targets glioma cells, impairs malignant growth, and enhances survival in mouse models in vivo

Tabernero Urbieta, María Aránzazu; Naus, Christian C; Medina Jiménez, José María; Bechberger, John; Sin, Wun Chey; Flores-Hernández, Raquel; Álvarez Vázquez, Andrea; Domínguez Prieto, Marta; Gutiérrez Pelaz, Sara; García Vicente, Laura; Talaverón Aguilocho, Rocío; Jaraíz-Rodríguez, Myriam

Connexin43 peptide, TAT-Cx43266–283, selectively targets glioma cells, impairs malignant growth, and enhances survival in mouse models in vivo

Background. Malignant gliomas are the most frequent primary brain tumors and remain among the most incur- able cancers. Although the role of the gap junction protein, connexin43 (Cx43), has been deeply investigated in malignant gliomas, no compounds have been reported with the ability to recapitulat...

ver descrição completa

Detalhes bibliográficos
Autores:	Tabernero Urbieta, María Aránzazu, Naus, Christian C, Medina Jiménez, José María, Bechberger, John, Sin, Wun Chey, Flores-Hernández, Raquel, Álvarez Vázquez, Andrea, Domínguez Prieto, Marta, Gutiérrez Pelaz, Sara, García Vicente, Laura, Talaverón Aguilocho, Rocío, Jaraíz-Rodríguez, Myriam
Formato:	artículo
Estado:	Versión publicada
Fecha de publicación:	2020
País:	España
Recursos:	Universidad de Salamanca (USAL)
Repositorio:	GREDOS. Repositorio Institucional de la Universidad de Salamanca
OAI Identifier:	oai:gredos.usal.es:10366/154676
Acesso em linha:	http://hdl.handle.net/10366/154676
Access Level:	acceso abierto
Palavra-chave:	cell-penetrating peptides connexin glioma Src Glioma Genes, src Connexins Cell-Penetrating Peptides 6310.03 Enfermedad

id	ES_84e718fee0f4dc2be7766d4d30d951cb
oai_identifier_str	oai:gredos.usal.es:10366/154676
network_acronym_str	ES
network_name_str	España
repository_id_str
spelling	Connexin43 peptide, TAT-Cx43266–283, selectively targets glioma cells, impairs malignant growth, and enhances survival in mouse models in vivoTabernero Urbieta, María AránzazuNaus, Christian CMedina Jiménez, José MaríaBechberger, JohnSin, Wun CheyFlores-Hernández, RaquelÁlvarez Vázquez, AndreaDomínguez Prieto, MartaGutiérrez Pelaz, SaraGarcía Vicente, LauraTalaverón Aguilocho, RocíoJaraíz-Rodríguez, Myriamcell-penetrating peptidesconnexingliomaSrcGliomaGenes, srcConnexinsCell-Penetrating Peptides6310.03 EnfermedadBackground. Malignant gliomas are the most frequent primary brain tumors and remain among the most incur- able cancers. Although the role of the gap junction protein, connexin43 (Cx43), has been deeply investigated in malignant gliomas, no compounds have been reported with the ability to recapitulate the tumor suppressor prop- erties of this protein in in vivo glioma models. Methods. TAT-Cx43266–283 a cell-penetrating peptide which mimics the effect of Cx43 on c-Src inhibition, was studied in orthotopic immunocompetent and immunosuppressed models of glioma. The effects of this peptide in brain cells were also analyzed. Results. While glioma stem cell malignant features were strongly affected byTAT-Cx43266–283, these properties were not significantly modified in neurons and astrocytes. Intraperitoneally administeredTAT-Cx43266–283 decreased the invasion of intracranial tumors generated by GL261 mouse glioma cells in immunocompetent mice. When human glioma stem cells were intracranially injected with TAT-Cx43266–283 into immunodeficient mice, there was reduced expression of the stemness markers nestin and Sox2 in human glioma cells at 7 days post-implantation. Consistent with the role of Sox2 as a transcription factor required for tumorigenicity,TAT-Cx43266–283 reduced the number and stemness of human glioma cells at 30 days post-implantation. Furthermore,TAT-Cx43266–283 enhanced the survival of immunocompetent mice bearing gliomas derived from murine glioma stem cells. Conclusion. TAT-Cx43266–283 reduces the growth, invasion, and progression of malignant gliomas and enhances the survival of glioma-bearing mice without exerting toxicity in endogenous brain cells, which suggests that this pep- tide could be considered as a new clinical therapy for high-grade gliomas.202420242020info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10366/154676reponame:GREDOS. Repositorio Institucional de la Universidad de Salamancainstname:Universidad de Salamanca (USAL)Inglésinfo:eu-repo/semantics/openAccessoai:gredos.usal.es:10366/1546762026-06-07T06:28:51Z
dc.title.none.fl_str_mv	Connexin43 peptide, TAT-Cx43266–283, selectively targets glioma cells, impairs malignant growth, and enhances survival in mouse models in vivo
title	Connexin43 peptide, TAT-Cx43266–283, selectively targets glioma cells, impairs malignant growth, and enhances survival in mouse models in vivo
spellingShingle	Connexin43 peptide, TAT-Cx43266–283, selectively targets glioma cells, impairs malignant growth, and enhances survival in mouse models in vivo Tabernero Urbieta, María Aránzazu cell-penetrating peptides connexin glioma Src Glioma Genes, src Connexins Cell-Penetrating Peptides 6310.03 Enfermedad
title_short	Connexin43 peptide, TAT-Cx43266–283, selectively targets glioma cells, impairs malignant growth, and enhances survival in mouse models in vivo
title_full	Connexin43 peptide, TAT-Cx43266–283, selectively targets glioma cells, impairs malignant growth, and enhances survival in mouse models in vivo
title_fullStr	Connexin43 peptide, TAT-Cx43266–283, selectively targets glioma cells, impairs malignant growth, and enhances survival in mouse models in vivo
title_full_unstemmed	Connexin43 peptide, TAT-Cx43266–283, selectively targets glioma cells, impairs malignant growth, and enhances survival in mouse models in vivo
title_sort	Connexin43 peptide, TAT-Cx43266–283, selectively targets glioma cells, impairs malignant growth, and enhances survival in mouse models in vivo
dc.creator.none.fl_str_mv	Tabernero Urbieta, María Aránzazu Naus, Christian C Medina Jiménez, José María Bechberger, John Sin, Wun Chey Flores-Hernández, Raquel Álvarez Vázquez, Andrea Domínguez Prieto, Marta Gutiérrez Pelaz, Sara García Vicente, Laura Talaverón Aguilocho, Rocío Jaraíz-Rodríguez, Myriam
author	Tabernero Urbieta, María Aránzazu
author_facet	Tabernero Urbieta, María Aránzazu Naus, Christian C Medina Jiménez, José María Bechberger, John Sin, Wun Chey Flores-Hernández, Raquel Álvarez Vázquez, Andrea Domínguez Prieto, Marta Gutiérrez Pelaz, Sara García Vicente, Laura Talaverón Aguilocho, Rocío Jaraíz-Rodríguez, Myriam
author_role	author
author2	Naus, Christian C Medina Jiménez, José María Bechberger, John Sin, Wun Chey Flores-Hernández, Raquel Álvarez Vázquez, Andrea Domínguez Prieto, Marta Gutiérrez Pelaz, Sara García Vicente, Laura Talaverón Aguilocho, Rocío Jaraíz-Rodríguez, Myriam
author2_role	author author author author author author author author author author author
dc.subject.none.fl_str_mv	cell-penetrating peptides connexin glioma Src Glioma Genes, src Connexins Cell-Penetrating Peptides 6310.03 Enfermedad
topic	cell-penetrating peptides connexin glioma Src Glioma Genes, src Connexins Cell-Penetrating Peptides 6310.03 Enfermedad
description	Background. Malignant gliomas are the most frequent primary brain tumors and remain among the most incur- able cancers. Although the role of the gap junction protein, connexin43 (Cx43), has been deeply investigated in malignant gliomas, no compounds have been reported with the ability to recapitulate the tumor suppressor prop- erties of this protein in in vivo glioma models. Methods. TAT-Cx43266–283 a cell-penetrating peptide which mimics the effect of Cx43 on c-Src inhibition, was studied in orthotopic immunocompetent and immunosuppressed models of glioma. The effects of this peptide in brain cells were also analyzed. Results. While glioma stem cell malignant features were strongly affected byTAT-Cx43266–283, these properties were not significantly modified in neurons and astrocytes. Intraperitoneally administeredTAT-Cx43266–283 decreased the invasion of intracranial tumors generated by GL261 mouse glioma cells in immunocompetent mice. When human glioma stem cells were intracranially injected with TAT-Cx43266–283 into immunodeficient mice, there was reduced expression of the stemness markers nestin and Sox2 in human glioma cells at 7 days post-implantation. Consistent with the role of Sox2 as a transcription factor required for tumorigenicity,TAT-Cx43266–283 reduced the number and stemness of human glioma cells at 30 days post-implantation. Furthermore,TAT-Cx43266–283 enhanced the survival of immunocompetent mice bearing gliomas derived from murine glioma stem cells. Conclusion. TAT-Cx43266–283 reduces the growth, invasion, and progression of malignant gliomas and enhances the survival of glioma-bearing mice without exerting toxicity in endogenous brain cells, which suggests that this pep- tide could be considered as a new clinical therapy for high-grade gliomas.
publishDate	2020
dc.date.none.fl_str_mv	2020 2024 2024
dc.type.none.fl_str_mv	info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion
format	article
status_str	publishedVersion
dc.identifier.none.fl_str_mv	http://hdl.handle.net/10366/154676
url	http://hdl.handle.net/10366/154676
dc.language.none.fl_str_mv	Inglés
language_invalid_str_mv	Inglés
dc.rights.none.fl_str_mv	info:eu-repo/semantics/openAccess
eu_rights_str_mv	openAccess
dc.source.none.fl_str_mv	reponame:GREDOS. Repositorio Institucional de la Universidad de Salamanca instname:Universidad de Salamanca (USAL)
instname_str	Universidad de Salamanca (USAL)
reponame_str	GREDOS. Repositorio Institucional de la Universidad de Salamanca
collection	GREDOS. Repositorio Institucional de la Universidad de Salamanca
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_	1869412258949365760
score	15,300724

Connexin43 peptide, TAT-Cx43266–283, selectively targets glioma cells, impairs malignant growth, and enhances survival in mouse models in vivo

Registos relacionados