Please use this identifier to cite or link to this item: http://bura.brunel.ac.uk/handle/2438/29516
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dc.contributor.authorLucotti, S-
dc.contributor.authorCerutti, C-
dc.contributor.authorSoyer, M-
dc.contributor.authorGil-Bernabé, AM-
dc.contributor.authorGomes, AL-
dc.contributor.authorAllen, PD-
dc.contributor.authorSmart, S-
dc.contributor.authorMarkelc, B-
dc.contributor.authorWatson, K-
dc.contributor.authorArmstrong, PC-
dc.contributor.authorMitchell, JA-
dc.contributor.authorWarner, TD-
dc.contributor.authorRidley, AJ-
dc.contributor.authorMuschel, RJ-
dc.date.accessioned2024-08-07T16:43:44Z-
dc.date.available2024-08-07T16:43:44Z-
dc.date.issued2019-03-25-
dc.identifierORCiD: Camilla Cerutti https://orcid.org/0000-0001-9426-686X-
dc.identifier.citationLucotti, S. et al. (2019) 'Aspirin blocks formation of metastatic intravascular niches by inhibiting platelet-derived COX-1/ thromboxane A<inf>2</inf>', Journal of Clinical Investigation, 129 (5), pp. 1845 - 1862. doi: 10.1172/JCI121985.en_US
dc.identifier.issn0021-9738-
dc.identifier.urihttps://bura.brunel.ac.uk/handle/2438/29516-
dc.descriptionSupplemental material is available online at: https://www.jci.org/articles/view/121985#sd .en_US
dc.description.abstractBecause metastasis is associated with the majority of cancer-related deaths, its prevention is a clinical aspiration. Prostanoids are a large family of bioactive lipids derived from the activity of cyclooxygenase-1 (COX-1) and COX-2. Aspirin impairs the biosynthesis of all prostanoids through the irreversible inhibition of both COX isoforms. Long-term administration of aspirin leads to reduced distant metastases in murine models and clinical trials, but the COX isoform, downstream prostanoid, and cell compartment responsible for this effect are yet to be determined. Here, we have shown that aspirin dramatically reduced lung metastasis through inhibition of COX-1 while the cancer cells remained intravascular and that inhibition of platelet COX-1 alone was sufficient to impair metastasis. Thromboxane A2 (TXA2) was the prostanoid product of COX-1 responsible for this antimetastatic effect. Inhibition of the COX-1/TXA2 pathway in platelets decreased aggregation of platelets on tumor cells, endothelial activation, tumor cell adhesion to the endothelium, and recruitment of metastasis-promoting monocytes/ macrophages, and diminished the formation of a premetastatic niche. Thus, platelet-derived TXA2 orchestrates the generation of a favorable intravascular metastatic niche that promotes tumor cell seeding and identifies COX-1/TXA2 signaling as a target for the prevention of metastasis.en_US
dc.description.sponsorshipRJM is funded by Cancer Research UK grant A1731. SL was the recipient of a Cancer Research UK Oxford Centre DPhil Prize Studentship (BBRTJW00).en_US
dc.format.extent1845 - 1862-
dc.format.mediumPrint-Electronic-
dc.language.isoen_USen_US
dc.publisherAmerican Society for Clinical Investigationen_US
dc.rightsCopyright: © 2019 Lucotti et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/.-
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/-
dc.titleAspirin blocks formation of metastatic intravascular niches by inhibiting platelet-derived COX-1/ thromboxane A<inf>2</inf>en_US
dc.title.alternativeAspirin blocks formation of metastatic intravascular niches by inhibiting platelet-derived COX-1/ thromboxane A2en_US
dc.typeArticleen_US
dc.date.dateAccepted2019-02-13-
dc.identifier.doihttps://doi.org/10.1172/JCI121985-
dc.relation.isPartOfJournal of Clinical Investigation-
pubs.issue5-
pubs.publication-statusPublished-
pubs.volume129-
dc.identifier.eissn1558-8238-
dc.rights.licensehttps://creativecommons.org/licenses/by/4.0/legalcode.en-
dc.rights.holderLucotti et al.-
Appears in Collections:Dept of Life Sciences Research Papers

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