Endothelial cell activation on 3D-matrices derived from PDGF-BB-stimulated fibroblasts is mediated by Snail1

Carcinomas, such as colon cancer, initiate their invasion by rescuing the innate plasticity of both epithelial cells and stromal cells. Although Snail is a transcriptional factor involved in the Epithelial-Mesenchymal Transition, in recent years, many studies have also identified the major role of S...

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Autores: Herrera, Alberto, Herrera, Mercedes, Guerra-Perez, Natalia, Galindo-Pumariño, Cristina, Larriba, María Jesús, García-Barberán, Vanesa, Gil, Beatriz, Giménez-Moyano, Sara, Ferreiro-Monteagudo, Reyes, Veguillas, Pilar, Candia, Antonio, Peña, Raúl|||0000-0002-1650-9720, Pinto, Jesús, García-Bermejo, Mª Laura, Muñoz, Alberto|||0000-0003-3890-4251, Garcia de Herreros, Antonio|||0000-0001-5270-0808, Bonilla, Félix, Carrato, Alfredo|||0000-0001-7749-8140, Peña, Cristina
Tipo de documento: artigo
Data de publicação:2018
País:España
Recursos:Universitat Autònoma de Barcelona
Repositório:Dipòsit Digital de Documents de la UAB
Idioma:inglês
OAI Identifier:oai:ddd.uab.cat:228023
Acesso em linha:https://ddd.uab.cat/record/228023
https://dx.doi.org/urn:doi:10.1038/s41389-018-0085-z
Access Level:Acceso aberto
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spelling Endothelial cell activation on 3D-matrices derived from PDGF-BB-stimulated fibroblasts is mediated by Snail1Herrera, AlbertoHerrera, MercedesGuerra-Perez, NataliaGalindo-Pumariño, CristinaLarriba, María JesúsGarcía-Barberán, VanesaGil, BeatrizGiménez-Moyano, SaraFerreiro-Monteagudo, ReyesVeguillas, PilarCandia, AntonioPeña, Raúl|||0000-0002-1650-9720Pinto, JesúsGarcía-Bermejo, Mª LauraMuñoz, Alberto|||0000-0003-3890-4251Garcia de Herreros, Antonio|||0000-0001-5270-0808Bonilla, FélixCarrato, Alfredo|||0000-0001-7749-8140Peña, CristinaCarcinomas, such as colon cancer, initiate their invasion by rescuing the innate plasticity of both epithelial cells and stromal cells. Although Snail is a transcriptional factor involved in the Epithelial-Mesenchymal Transition, in recent years, many studies have also identified the major role of Snail in the activation of Cancer-Associated Fibroblast (CAF) cells and the remodeling of the extracellular matrix. In CAFs, Platelet-derived growth factor (PDGF) receptor signaling is a major functional determinant. High expression of both SNAI1 and PDGF receptors is associated with poor prognosis in cancer patients, but the mechanism(s) that underlie these connections are not understood. In this study, we demonstrate that PDGF-activated fibroblasts stimulate extracellular matrix (ECM) fiber remodeling and deposition. Furthermore, we describe how SNAI1, through the FAK pathway, is a necessary factor for ECM fiber organization. The parallel-oriented fibers are used by endothelial cells as "tracks", facilitating their activation and the creation of tubular structures mimicking in vivo capillary formation. Accordingly, Snail1 expression in fibroblasts was required for the co-adjuvant effect of these cells on matrix remodeling and neoangiogenesis when co-xenografted in nude mice. Finally, in tumor samples from colorectal cancer patients a direct association between stromal SNAI1 expression and the endothelial marker CD34 was observed. In summary, our results advance the understanding of PDGF/SNAI1-activated CAFs in matrix remodeling and angiogenesis stimulation.Universitat Autònoma de Barcelona 22018-01-0120182018-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/228023https://dx.doi.org/urn:doi:10.1038/s41389-018-0085-zreponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengInstituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI12-02037Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI12-01635Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI15-02101Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI17-01847Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 RD12-0036-0041Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 RD12-0036-0021Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PIE15-00008Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 FEDER/RD12-0036-0005Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 SAF2013-48849-C2-1-RAgencia Estatal de Investigación https://doi.org/10.13039/501100011033 SAF2016-76377-Ropen accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:2280232026-06-06T12:50:31Z
dc.title.none.fl_str_mv Endothelial cell activation on 3D-matrices derived from PDGF-BB-stimulated fibroblasts is mediated by Snail1
title Endothelial cell activation on 3D-matrices derived from PDGF-BB-stimulated fibroblasts is mediated by Snail1
spellingShingle Endothelial cell activation on 3D-matrices derived from PDGF-BB-stimulated fibroblasts is mediated by Snail1
Herrera, Alberto
title_short Endothelial cell activation on 3D-matrices derived from PDGF-BB-stimulated fibroblasts is mediated by Snail1
title_full Endothelial cell activation on 3D-matrices derived from PDGF-BB-stimulated fibroblasts is mediated by Snail1
title_fullStr Endothelial cell activation on 3D-matrices derived from PDGF-BB-stimulated fibroblasts is mediated by Snail1
title_full_unstemmed Endothelial cell activation on 3D-matrices derived from PDGF-BB-stimulated fibroblasts is mediated by Snail1
title_sort Endothelial cell activation on 3D-matrices derived from PDGF-BB-stimulated fibroblasts is mediated by Snail1
dc.creator.none.fl_str_mv Herrera, Alberto
Herrera, Mercedes
Guerra-Perez, Natalia
Galindo-Pumariño, Cristina
Larriba, María Jesús
García-Barberán, Vanesa
Gil, Beatriz
Giménez-Moyano, Sara
Ferreiro-Monteagudo, Reyes
Veguillas, Pilar
Candia, Antonio
Peña, Raúl|||0000-0002-1650-9720
Pinto, Jesús
García-Bermejo, Mª Laura
Muñoz, Alberto|||0000-0003-3890-4251
Garcia de Herreros, Antonio|||0000-0001-5270-0808
Bonilla, Félix
Carrato, Alfredo|||0000-0001-7749-8140
Peña, Cristina
author Herrera, Alberto
author_facet Herrera, Alberto
Herrera, Mercedes
Guerra-Perez, Natalia
Galindo-Pumariño, Cristina
Larriba, María Jesús
García-Barberán, Vanesa
Gil, Beatriz
Giménez-Moyano, Sara
Ferreiro-Monteagudo, Reyes
Veguillas, Pilar
Candia, Antonio
Peña, Raúl|||0000-0002-1650-9720
Pinto, Jesús
García-Bermejo, Mª Laura
Muñoz, Alberto|||0000-0003-3890-4251
Garcia de Herreros, Antonio|||0000-0001-5270-0808
Bonilla, Félix
Carrato, Alfredo|||0000-0001-7749-8140
Peña, Cristina
author_role author
author2 Herrera, Mercedes
Guerra-Perez, Natalia
Galindo-Pumariño, Cristina
Larriba, María Jesús
García-Barberán, Vanesa
Gil, Beatriz
Giménez-Moyano, Sara
Ferreiro-Monteagudo, Reyes
Veguillas, Pilar
Candia, Antonio
Peña, Raúl|||0000-0002-1650-9720
Pinto, Jesús
García-Bermejo, Mª Laura
Muñoz, Alberto|||0000-0003-3890-4251
Garcia de Herreros, Antonio|||0000-0001-5270-0808
Bonilla, Félix
Carrato, Alfredo|||0000-0001-7749-8140
Peña, Cristina
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universitat Autònoma de Barcelona
description Carcinomas, such as colon cancer, initiate their invasion by rescuing the innate plasticity of both epithelial cells and stromal cells. Although Snail is a transcriptional factor involved in the Epithelial-Mesenchymal Transition, in recent years, many studies have also identified the major role of Snail in the activation of Cancer-Associated Fibroblast (CAF) cells and the remodeling of the extracellular matrix. In CAFs, Platelet-derived growth factor (PDGF) receptor signaling is a major functional determinant. High expression of both SNAI1 and PDGF receptors is associated with poor prognosis in cancer patients, but the mechanism(s) that underlie these connections are not understood. In this study, we demonstrate that PDGF-activated fibroblasts stimulate extracellular matrix (ECM) fiber remodeling and deposition. Furthermore, we describe how SNAI1, through the FAK pathway, is a necessary factor for ECM fiber organization. The parallel-oriented fibers are used by endothelial cells as "tracks", facilitating their activation and the creation of tubular structures mimicking in vivo capillary formation. Accordingly, Snail1 expression in fibroblasts was required for the co-adjuvant effect of these cells on matrix remodeling and neoangiogenesis when co-xenografted in nude mice. Finally, in tumor samples from colorectal cancer patients a direct association between stromal SNAI1 expression and the endothelial marker CD34 was observed. In summary, our results advance the understanding of PDGF/SNAI1-activated CAFs in matrix remodeling and angiogenesis stimulation.
publishDate 2018
dc.date.none.fl_str_mv 2
2018-01-01
2018
2018-01-01
dc.type.none.fl_str_mv Article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://ddd.uab.cat/record/228023
https://dx.doi.org/urn:doi:10.1038/s41389-018-0085-z
url https://ddd.uab.cat/record/228023
https://dx.doi.org/urn:doi:10.1038/s41389-018-0085-z
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI12-02037
Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI12-01635
Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI15-02101
Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI17-01847
Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 RD12-0036-0041
Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 RD12-0036-0021
Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PIE15-00008
Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 FEDER/RD12-0036-0005
Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 SAF2013-48849-C2-1-R
Agencia Estatal de Investigación https://doi.org/10.13039/501100011033 SAF2016-76377-R
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Dipòsit Digital de Documents de la UAB
instname:Universitat Autònoma de Barcelona
instname_str Universitat Autònoma de Barcelona
reponame_str Dipòsit Digital de Documents de la UAB
collection Dipòsit Digital de Documents de la UAB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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