Liver sinusoidal endothelial cell ICAM-1 mediated tumor/endothelial crosstalk drives the development of liver metastasis by initiating inflammatory and angiogenic responses
dc.contributor.author | Benedicto García, Aitor | |
dc.contributor.author | Herrero, Alba | |
dc.contributor.author | Romayor Arredondo, Irene | |
dc.contributor.author | Márquez Clavijo, Joana | |
dc.contributor.author | Smedsrod, Bard | |
dc.contributor.author | Olaso Montero, Elvira | |
dc.contributor.author | Arteta Ruiz, Beatriz | |
dc.date.accessioned | 2020-01-13T09:25:11Z | |
dc.date.available | 2020-01-13T09:25:11Z | |
dc.date.issued | 2019-09-11 | |
dc.identifier.citation | Scientific Reports 9 : (2019) // Article ID 13111 | es_ES |
dc.identifier.issn | 2045-2322 | |
dc.identifier.uri | http://hdl.handle.net/10810/37729 | |
dc.description.abstract | The prometastatic stroma generated through tumor cells/host cells interaction is critical for metastatic growth. To elucidate the role of ICAM-1 on the crosstalk between tumor and primary liver sinusoidal endothelial cells (LSECs) and hepatic stellate cells (HSCs), implicated in tumor adhesion and angiogenesis, we performed in vitro cocultures and an in vivo model of liver metastasis of colorectal cancer (CRC). ICAM-1 blockade in the LSECs decreased the adhesion and transmigration of tumor cells through an LSEC in vitro and vivo. Cocultures of C26 cells and LSECs contained higher amounts of IL-1 beta, IL-6, PGE-2, TNF-alpha and ICAM-1 than monocultures. C26 cells incubated with sICAM-1 secreted higher amounts of PGE-2, IL-6, VEGF, and MMPs, while enhanced the migration of LSECs and HSCs. HSCs cultures activated by media from C26 cells pretreated with sICAM-1 contained the largest amounts of VEGF and MMPs. C26 cell activation with sICAM-1 enhanced their metastasizing potential in vivo, while tumor LFA-1 blockade reduced tumor burden and LSECs and HSC-derived myofibroblasts recruitment. In vivo ICAM-1 silencing produced similar results. These findings uncover LSEC ICAM-1 as a mediator of the CRC metastatic cascade in the liver and identifies it as target for the inhibition of liver colonization and metastatic progression. | es_ES |
dc.description.sponsorship | This work has been supported by a predoctoral grant from the University of the Basque Country to the principal author and from the Department of Industry and Research of the Basque Government SAIOTEK S-PE12UN075 and S-PE11UN043 to BA, and IT-487-09 to EO. | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Nature Publishing | es_ES |
dc.rights | info:eu-repo/semantics/openAccess | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es/ | * |
dc.subject | plasminogen-activator expression | es_ES |
dc.subject | hepatic stellate cells | es_ES |
dc.subject | NF-kappa B | es_ES |
dc.subject | cancer | es_ES |
dc.subject | tumor | es_ES |
dc.subject | adhesion | es_ES |
dc.subject | cytokines | es_ES |
dc.subject | immunity | es_ES |
dc.subject | receptor | es_ES |
dc.subject | alpha | es_ES |
dc.title | Liver sinusoidal endothelial cell ICAM-1 mediated tumor/endothelial crosstalk drives the development of liver metastasis by initiating inflammatory and angiogenic responses | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.rights.holder | 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. (CC BY 4.0) | es_ES |
dc.rights.holder | Atribución 3.0 España | * |
dc.relation.publisherversion | https://www.nature.com/articles/s41598-019-49473-7 | es_ES |
dc.identifier.doi | 10.1038/s41598-019-49473-7 | |
dc.departamentoes | Biología celular e histología | es_ES |
dc.departamentoeu | Zelulen biologia eta histologia | es_ES |
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