Snail1 expression in endothelial cells controls growth, angiogenesis and differentiation of breast tumors

Mostra el registre complet Registre parcial de l'ítem

• dc.contributor.author Cabrerizo Granados, David, 1993-
• dc.contributor.author Peña Arranz, Raúl, 1976-
• dc.contributor.author Palacios, Laura
• dc.contributor.author Carrillo-Bosch, Laura
• dc.contributor.author Lloreta, Josep, 1958-
• dc.contributor.author Comerma Blesa, Laura, 1983-
• dc.contributor.author Iglesias Coma, Mar
• dc.contributor.author García de Herreros, Antonio
• dc.date.accessioned 2022-03-21T11:54:31Z
• dc.date.available 2022-03-21T11:54:31Z
• dc.date.issued 2021
• dc.description.abstract Snail1 is a transcriptional factor required for epithelial to mesenchymal transition and activation of cancer-associated fibroblasts (CAF). Apart from that, tumor endothelial cells also express Snail1. Here, we have unraveled the role of Snail1 in this tissue in a tumorigenic context. Methods: We generated transgenic mice with an endothelial-specific and inducible Snail1 depletion. This murine line was crossed with MMTV-PyMT mice that develop mammary gland tumors and the consequence of Snail1 depletion in the endothelium were investigated. We also interfere Snail1 expression in cultured endothelial cells. Results: Specific Snail1 depletion in the endothelium of adult mice does not promote an overt phenotype; however, it delays the formation of mammary gland tumors in MMTV-PyMT mice. These effects are associated to the inability of Snail1-deficient endothelial cells to undergo angiogenesis and to enhance CAF activation in a paracrine manner. Moreover, tumors generated in mice with endothelium-specific Snail1 depletion are less advanced and show a papillary phenotype. Similar changes on onset and tumor morphology are observed by pretreatment of MMTV-PyMT mice with the angiogenic inhibitor Bevacizumab. Human breast papillary carcinomas exhibit a lower angiogenesis and present lower staining of Snail1, both in endothelial and stromal cells, compared with other breast neoplasms. Furthermore, human breast tumors datasets show a strong correlation between Snail1 expression and high angiogenesis. Conclusion: These findings show a novel role for Snail1 in endothelial cell activation and demonstrate that these cells impact not only on angiogenesis, but also on tumor onset and phenotype.
• dc.description.sponsorship This study was funded by grants awarded to AGH by Agencia Estatal de Investigación (AEI) and Fondos FEDER (SAF2016-76461-R) and AEI (PID2019-104695RB-100/AEI/10.13039/501100011033). We also acknowledge support from the Instituto Carlos III / FEDER (PIE15/00008; PT17/0015/0011) and the "Xarxa de Bancs de tumors” sponsored by Pla Director d'Oncologia de Catalunya (XBTC). DCG was recipient of an FPU predoctoral fellowship from Ministerio de Educación
• dc.format.mimetype application/pdf
• dc.identifier.citation Cabrerizo-Granados D, Peña R, Palacios L, Carrillo-Bosch L, Lloreta-Trull J, Cormema L, Iglesias M et al. Snail1 expression in endothelial cells controls growth, angiogenesis and differentiation of breast tumors. Theranostics. 2021 Jun 16;11(16):7671-7684. DOI: 10.7150/thno.61881
• dc.identifier.doi http://dx.doi.org/10.7150/thno.61881
• dc.identifier.issn 1838-7640
• dc.identifier.uri http://hdl.handle.net/10230/52737
• dc.language.iso eng
• dc.publisher Ivyspring International Publisher
• dc.rights © 2022 Ivyspring International Publisher. Under the Creative Commons Attribution 4.0 International License (CC-BY license). The Open Access statement is: “This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.” Authors retain copyright of the article, and grant Ivyspring International Publisher a license to publish, use, reproduce and distribute the article and the material contained therein throughout the world in all languages and in all media (now or hereafter known)
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri https://creativecommons.org/licenses/by/4.0/
• dc.subject.other Càncer
• dc.subject.other Tumors
• dc.subject.other Genètica
• dc.subject.other Cèl·lules endotelials
• dc.subject.other Proteïnes
• dc.title Snail1 expression in endothelial cells controls growth, angiogenesis and differentiation of breast tumors
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion