Web of Science: 21 citas, Scopus: 26 citas, Google Scholar: citas,
Endothelial cell activation on 3D-matrices derived from PDGF-BB-stimulated fibroblasts is mediated by Snail1
Herrera, Alberto (Hospital Universitario Puerta de Hierro Majadahonda (Madrid))
Herrera, Mercedes (Karolinska Institutet (Estocolm, Suècia). Department of Oncology and Pathology)
Guerra-Perez, Natalia (Instituto Ramón y Cajal de Investigación Sanitaria (Madrid))
Galindo-Pumariño, Cristina (Instituto Ramón y Cajal de Investigación Sanitaria (Madrid))
Larriba, María Jesús (Universidad Autónoma de Madrid. Instituto de Investigaciones Biomédicas "Alberto Sols")
García-Barberán, Vanesa (Hospital Clínico San Carlos (Madrid))
Gil, Beatriz (Instituto de Investigación Sanitaria Hospital 12 de Octubre (i+12))
Giménez-Moyano, Sara (Instituto Ramón y Cajal de Investigación Sanitaria (Madrid))
Ferreiro-Monteagudo, Reyes (Instituto Ramón y Cajal de Investigación Sanitaria (Madrid))
Veguillas, Pilar (Hospital Universitario de Guadalajara)
Candia, Antonio (Hospital Universitario de Guadalajara)
Peña, Raúl (Institut Hospital del Mar d'Investigacions Mèdiques)
Pinto, Jesús (Hospital Virgen de la Concha (Zamora))
García-Bermejo, Mª Laura (Instituto de Investigación Sanitaria Hospital 12 de Octubre (i+12))
Munoz, Alberto (Universidad Autónoma de Madrid. Instituto de Investigaciones Biomédicas "Alberto Sols")
Garcia de Herreros, Antonio (Institut Hospital del Mar d'Investigacions Mèdiques)
Bonilla, Félix (Centro de Estudios Biosanitarios, Madrid, Spain)
Carrato, Alfredo (Hospital Universitario Ramón y Cajal (Madrid))
Peña, Cristina (Instituto Ramón y Cajal de Investigación Sanitaria (Madrid))
Universitat Autònoma de Barcelona

Fecha: 2018
Resumen: 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.
Ayudas: Instituto de Salud Carlos III PI12-02037
Instituto de Salud Carlos III PI12-01635
Instituto de Salud Carlos III PI15-02101
Instituto de Salud Carlos III PI17-01847
Instituto de Salud Carlos III RD12-0036-0041
Instituto de Salud Carlos III RD12-0036-0021
Instituto de Salud Carlos III PIE15-00008
Instituto de Salud Carlos III FEDER/RD12-0036-0005
Ministerio de Economía y Competitividad SAF2013-48849-C2-1-R
Ministerio de Economía y Competitividad SAF2016-76377-R
Nota: Altres ajuts: This research is supported by 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 the Instituto de Salud Carlos III-FEDER and 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.
Derechos: Aquest 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. Creative Commons
Lengua: Anglès
Documento: Article ; recerca ; Versió publicada
Publicado en: Oncogenesis, Vol. 7 (september 2018) , ISSN 2157-9024

DOI: 10.1038/s41389-018-0085-z
PMID: 30250018


15 p, 4.2 MB

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