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dc.contributor.authorBenedicto García, Aitor
dc.contributor.authorMárquez Clavijo, Joana
dc.contributor.authorHerrero, Alba
dc.contributor.authorOlaso Montero, Elvira
dc.contributor.authorKolaczkowska, Elzbieta
dc.contributor.authorArteta Ruiz, Beatriz
dc.date.accessioned2019-04-05T07:37:42Z
dc.date.available2019-04-05T07:37:42Z
dc.date.issued2017-12-06
dc.identifier.citationBMC Cancer17 : (2017) // Article ID 827es_ES
dc.identifier.issn1471-2407
dc.identifier.urihttp://hdl.handle.net/10810/32349
dc.description.abstractBackground: Lymphocyte Function-Associated Antigen-1 (LFA-1; CD18/CD11a) is one of the main adhesion molecules used by immune cells to infiltrate the liver under inflammatory conditions. Recently, the expression of this integrin has also been reported on several solid tumors, including colorectal cancer. However, its functional role in the metastatic progression to the liver remains unknown. Using in vitro assays and an experimental orthotopic in vivo model of liver metastasis, we aimed to elucidate the role of tumor LFA-1 in the metastatic progression by means of the partial depletion of the beta(2) subunit of LFA-1, required for integrin activation, firm adhesion and signaling. Methods: To do so, we evaluated the effects of beta(2)reduction on the murine colon carcinoma C26 cell line on their pro-metastatic features in vitro and their metastatic potential in vivo in a mouse model of colon carcinoma metastasis to the liver. Results: The reduction in beta(2) integrin expression correlated with a slower proliferation, and a reduced adhesion and migration of C26 cells in an in vitro setting. Additionally, tumor cells with a reduced in beta(2) integrin expression were unable to activate the liver sinusoidal endothelial cells (LSECs). This resulted in a recovery of the cytotoxic potential of liver lymphocytes which is compromised by LSECs activated by C26 cells. This was related to the abrogation of RNA expression of inflammatory and angiogenic cytokines by C26 cells after their activation with sICAM-1, the main ligand of beta(2)aL. Furthermore, in vivo tumor cell retention and metastasis were profoundly reduced, along with a decrease in the recruitment and infiltration of myeloid derived suppressor cells (MDSCs) and lymphocytes to the liver. Conclusion: Taken together, our findings uncovered the modulatory role for the tumor beta(2)subunit of the LFA-1 integrin in the metastatic progression of colorectal cancer to the liver by impairing activation of liver endothelium and thus, the local immune response in the liver. Besides, this integrin also showed to be critical in vivo for tumor cell retention, cytokine release, leukocyte recruitment and metastasis development. These data support a therapeutical potential of the integrin LFA-1 as a target for the treatment of colorectal liver metastasis.es_ES
dc.description.sponsorshipThis study was financially supported in part by a pre-doctoral grant from the University of the Basque Country to A.B. and by funds from the Basque Government-Saiotek to B.A.es_ES
dc.language.isoenges_ES
dc.publisherBiomed Centrales_ES
dc.rightsinfo:eu-repo/semantics/openAccesses_ES
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/es/*
dc.subjectliver metastasises_ES
dc.subjectcolorectal canceres_ES
dc.subjectbeta(2) integrines_ES
dc.subjectLFA-1es_ES
dc.subjectICAM-1es_ES
dc.subjectimmune responsees_ES
dc.subjectendothelial cellses_ES
dc.subjecttumor microenvironmentes_ES
dc.subjectadhesion moleculeses_ES
dc.subjectsuppressor-cellses_ES
dc.subjectcyclooxygenase-2 inhibitores_ES
dc.subjectendothelial-cellses_ES
dc.subjectmediated adhesiones_ES
dc.subjectmyeloma cellses_ES
dc.subjectup-regulationes_ES
dc.subjectt-cellses_ES
dc.subjectlfa-1es_ES
dc.subjectprogressiones_ES
dc.titleDecreased expression of the β2 integrin on tumor cells is associated with a reduction in liver metastasis of colorectal cancer in micees_ES
dc.typeinfo:eu-repo/semantics/articlees_ES
dc.rights.holderThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided 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 Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.es_ES
dc.rights.holderAtribución 3.0 España*
dc.relation.publisherversionhttps://bmccancer.biomedcentral.com/articles/10.1186/s12885-017-3823-2es_ES
dc.identifier.doi10.1186/s12885-017-3823-2
dc.departamentoesBiología celular e histologíaes_ES
dc.departamentoeuZelulen biologia eta histologiaes_ES


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This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided 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 Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Except where otherwise noted, this item's license is described as This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided 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 Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.