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...

Full description

Bibliographic Details
Authors: 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, Pinto, Jesús, García-Bermejo, Mª Laura, Muñoz, Alberto, García de Herreros, Antonio, Bonilla, Félix, Carrato, Alfredo, Peña, Cristina
Format: article
Status:Published version
Publication Date:2018
Country:España
Institution:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repository:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10230/37032
Online Access:http://hdl.handle.net/10230/37032
http://dx.doi.org/10.1038/s41389-018-0085-z
Access Level:Open access
Keyword:Cancer microenvironment
Colorectal cancer
Tumour angiogenesis
id ES_19bcb200510ea9ff92b6bfed022b8a35
oai_identifier_str oai:recercat.cat:10230/37032
network_acronym_str ES
network_name_str España
repository_id_str
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
Cancer microenvironment
Colorectal cancer
Tumour angiogenesis
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
Pinto, Jesús
García-Bermejo, Mª Laura
Muñoz, Alberto
García de Herreros, Antonio
Bonilla, Félix
Carrato, Alfredo
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
Pinto, Jesús
García-Bermejo, Mª Laura
Muñoz, Alberto
García de Herreros, Antonio
Bonilla, Félix
Carrato, Alfredo
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
Pinto, Jesús
García-Bermejo, Mª Laura
Muñoz, Alberto
García de Herreros, Antonio
Bonilla, Félix
Carrato, Alfredo
Peña, Cristina
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Cancer microenvironment
Colorectal cancer
Tumour angiogenesis
topic Cancer microenvironment
Colorectal cancer
Tumour angiogenesis
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 2018
2019
2019
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/10230/37032
http://dx.doi.org/10.1038/s41389-018-0085-z
url http://hdl.handle.net/10230/37032
http://dx.doi.org/10.1038/s41389-018-0085-z
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Oncogenesis. 2018; 7(9):76
info:eu-repo/grantAgreement/ES/3PN/SAF2010-20750
info:eu-repo/grantAgreement/ES/1PE/SAF2016-76461-R
info:eu-repo/grantAgreement/ES/1PE/SAF2013-48849-C2-1-R
info:eu-repo/grantAgreement/ES/1PE/SAF2016-76377-R
dc.rights.none.fl_str_mv http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Nature Research
publisher.none.fl_str_mv Nature Research
dc.source.none.fl_str_mv reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869404063550930944
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, RaúlPinto, JesúsGarcía-Bermejo, Mª LauraMuñoz, AlbertoGarcía de Herreros, AntonioBonilla, FélixCarrato, AlfredoPeña, CristinaCancer microenvironmentColorectal cancerTumour angiogenesisCarcinomas, 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.This research is supported by PI12/02037, PI12/01635, PI15/02101, PI17/01847, RD12/0036/0041 and RD12/0036/0021, and PIE15/00008 from the Instituto de Salud Carlos III- by Fondo Europeo de Desarrollo Regional (FEDER); by “CIBER de Cáncer”, CB16/12/00273, CB16/1200301, and CB16/12/00446, from the Instituto de Salud Carlos III-FEDER; by the Fundación Científica AECC (a multifaceted approach to target pancreatic cancer); by SAF2010-20750 and SAF2016-76461-R from the Ministerio de Economía y Competitividad of Spain-FEDER; by S2010/BMD-2344 from the Comunidad de Madrid; and by the Fundación Banco Santander. A.G.de.H.’ laboratory is supported by RD12/0036/0005 (from the Instituto de Salud Carlos III-FEDER) and SAF2013-48849-C2-1-R and SAF2016-76377-R (from the Ministerio de Economía y Competitividad of Spain-FEDER). C.P. is a recipient of a Miguel Servet Contract from the Instituto de Salud Carlos III. M. Eaude helped with the English text. We thank lab members for help and advice throughout this research.Nature Research201920192018info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/37032http://dx.doi.org/10.1038/s41389-018-0085-zreponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésOncogenesis. 2018; 7(9):76info:eu-repo/grantAgreement/ES/3PN/SAF2010-20750info:eu-repo/grantAgreement/ES/1PE/SAF2016-76461-Rinfo:eu-repo/grantAgreement/ES/1PE/SAF2013-48849-C2-1-Rinfo:eu-repo/grantAgreement/ES/1PE/SAF2016-76377-R© The Author(s) 2018. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.http://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:10230/370322026-05-29T05:05:01Z
score 15,81155

Similar Items