dc.contributor.author | Herrero Alonso, Alba | |
dc.contributor.author | Benedicto García, Aitor | |
dc.contributor.author | Romayor Arredondo, Irene | |
dc.contributor.author | Olaso Montero, Elvira | |
dc.contributor.author | Arteta Ruiz, Beatriz | |
dc.date.accessioned | 2021-06-11T10:21:40Z | |
dc.date.available | 2021-06-11T10:21:40Z | |
dc.date.issued | 2021-05 | |
dc.identifier.citation | Biomolecules And Therapeutics 29(2) : 342-351 (2021) | es_ES |
dc.identifier.issn | 1976-9148 | |
dc.identifier.issn | 2005-4483 | |
dc.identifier.uri | http://hdl.handle.net/10810/51845 | |
dc.description.abstract | Liver colonization is initiated through the interplay between tumor cells and adhesion molecules present in liver sinusoidal endothelial cells (LSECs). This crosstalk stimulates tumor COX-2 upregulation and PGE 2 secretion. To elucidate the role of the LSEC intercellular adhesion molecule-1 (ICAM-1) in the prometastatic response exerted by tumor and stromal COX-2, we utilized celecoxib (CLX) as a COX-2 inhibitory agent. We analyzed the in vitro proliferative and secretory responses of murine C26 colorectal cancer (CRC) cells to soluble ICAM-1 (sICAM-1), cultured alone or with LSECs, and their effect on LSEC and hepatic stellate cell (HSC) migration and in vivo liver metastasis. CLX reduced sICAM-1-stimulated COX-2 activation and PGE 2 secretion in C26 cells cultured alone or cocultured with LSECs. Moreover, CLX abrogated sICAM-1-induced C26 cell proliferation and C26 secretion of promigratory factors for LSECs and HSCs. Interestingly, CLX reduced the protumoral response of HSC, reducing their migratory potential when stimulated with C26 secretomes and impairing their secretion of chemotactic factors for LSECs and C26 cells and proliferative factors for C26 cells. In vivo, CLX abrogated the prometastatic ability of sICAM-1-activated C26 cells while reducing liver metastasis. COX-2 inhibition blocked the creation of a favorable tumor microenvironment (TME) by hindering the intratumoral recruitment of activated HSCs and macrophages in addition to the accumulation of fibrillar collagen. These results point to COX-2 being a key modulator of processes initiated by host ICAM-1 during tumor cell/LSEC/HSC crosstalk, leading to the creation of a prometastatic TME in the liver. | es_ES |
dc.description.sponsorship | This work was supported by the Department of Industry and Research of the Basque Government SAIOTEK SPE12UN075 and S-PE11UN043 to B.A., IT-487-09 to E.O., and by the Spanish Science and Technology Ministry MINECOR18/P32. | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Korean Society of Applied Pharmacology | es_ES |
dc.rights | info:eu-repo/semantics/openAccess | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by-nc/3.0/es/ | * |
dc.subject | liver metastasis | es_ES |
dc.subject | tumor microenvironment | es_ES |
dc.subject | cyclooxygenase-2 | es_ES |
dc.subject | hepatic stellate cells | es_ES |
dc.subject | CAF | es_ES |
dc.subject | colorectal cancer | es_ES |
dc.subject | endothelial growth-factor | es_ES |
dc.subject | suppressor-cells | es_ES |
dc.subject | tumor | es_ES |
dc.subject | expression | es_ES |
dc.subject | VEGF | es_ES |
dc.subject | proliferation | es_ES |
dc.subject | invasiveness | es_ES |
dc.title | Inhibition of COX-2 Impairs Colon Cancer Liver Metastasis through Reduced Stromal Cell Reaction | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.rights.holder | This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (CC BY-NC 4.0) | es_ES |
dc.rights.holder | Atribución-NoComercial 3.0 España | * |
dc.relation.publisherversion | https://www.biomolther.org/journal/view.html?volume=29&number=3&spage=342&year=2021 | es_ES |
dc.identifier.doi | 10.4062/biomolther.2020.160 | |
dc.departamentoes | Biología celular e histología | es_ES |
dc.departamentoeu | Zelulen biologia eta histologia | es_ES |