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dc.contributor.authorPanigrahy, Dipak
dc.contributor.authorEdin, Matthew L.
dc.contributor.authorLee, Craig R.
dc.contributor.authorHuang, Sui
dc.contributor.authorBielenberg, Diane
dc.contributor.authorButterfield, Catherine E.
dc.contributor.authorBarnés, Carmen M.
dc.contributor.authorMammoto, Akiko
dc.contributor.authorMammoto, Tadanori
dc.contributor.authorLuria, Ayala
dc.contributor.authorBenny, Ofra
dc.contributor.authorChaponis, Deviney M.
dc.contributor.authorDudley, Andrew C.
dc.contributor.authorGreene, Emily R.
dc.contributor.authorVergilio, Jo-Anne
dc.contributor.authorPietramaggiori, Giorgio
dc.contributor.authorScherer-Pietramaggiori, Sandra S.
dc.contributor.authorShort, Sarah M.
dc.contributor.authorSeth, Meetu
dc.contributor.authorLih, Fred B.
dc.contributor.authorTomer, Kenneth B.
dc.contributor.authorYang, Jun
dc.contributor.authorSchwendener, Reto A.
dc.contributor.authorHammock, Bruce D.
dc.contributor.authorFalck, John R.
dc.contributor.authorManthati, Vijaya L.
dc.contributor.authorIngber, Donald Elliot
dc.contributor.authorKaipainen, Arja
dc.contributor.authorD'Amore, Patricia Ann
dc.contributor.authorKieran, Mark W.
dc.contributor.authorZeldin, Darryl C.
dc.date.accessioned2018-03-07T18:57:59Z
dc.date.issued2012
dc.identifierQuick submit: 2017-06-23T15:12:05-0400
dc.identifier.citationPanigrahy, Dipak, Matthew L. Edin, Craig R. Lee, Sui Huang, Diane R. Bielenberg, Catherine E. Butterfield, Carmen M. Barnés, et al. 2012. “Epoxyeicosanoids Stimulate Multiorgan Metastasis and Tumor Dormancy Escape in Mice.” Journal of Clinical Investigation 122 (1) (January 3): 178–191. doi:10.1172/jci58128.en_US
dc.identifier.issn0021-9738en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:34902775
dc.description.abstractEpoxyeicosatrienoic acids (EETs) are small molecules produced by cytochrome P450 epoxygenases. They are lipid mediators that act as autocrine or paracrine factors to regulate inflammation and vascular tone. As a result, drugs that raise EET levels are in clinical trials for the treatment of hypertension and many other diseases. However, despite their pleiotropic effects on cells, little is known about the role of these epoxyeicosanoids in cancer. Here, using genetic and pharmacological manipulation of endogenous EET levels, we demonstrate that EETs are critical for primary tumor growth and metastasis in a variety of mouse models of cancer. Remarkably, we found that EETs stimulated extensive multiorgan metastasis and escape from tumor dormancy in several tumor models. This systemic metastasis was not caused by excessive primary tumor growth but depended on endothelium-derived EETs at the site of metastasis. Administration of synthetic EETs recapitulated these results, while EET antagonists suppressed tumor growth and metastasis, demonstrating in vivo that pharmacological modulation of EETs can affect cancer growth. Furthermore, inhibitors of soluble epoxide hydrolase (sEH), the enzyme that metabolizes EETs, elevated endogenous EET levels and promoted primary tumor growth and metastasis. Thus, our data indicate a central role for EETs in tumorigenesis, offering a mechanistic link between lipid signaling and cancer and emphasizing the critical importance of considering possible effects of EET-modulating drugs on cancer.en_US
dc.language.isoen_USen_US
dc.publisherAmerican Society for Clinical Investigationen_US
dc.relation.isversionof10.1172/jci58128en_US
dc.relation.hasversionhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3248288/en_US
dash.licenseLAA
dc.titleEpoxyeicosanoids stimulate multiorgan metastasis and tumor dormancy escape in miceen_US
dc.typeJournal Articleen_US
dc.date.updated2017-06-23T19:12:07Z
dc.description.versionVersion of Recorden_US
dc.relation.journalJournal of Clinical Investigationen_US
dash.depositing.authorD'Amore, Patricia Ann
dc.date.available2011
dc.date.available2018-03-07T18:57:59Z
dc.identifier.doi10.1172/jci58128*
workflow.legacycommentscat.completeen_US
dash.authorsorderedfalse
dash.contributor.affiliatedBielenberg, Diane
dash.contributor.affiliatedPanigrahy, Dipak
dash.contributor.affiliatedKieran, Mark W.
dash.contributor.affiliatedD'Amore, Patricia
dash.contributor.affiliatedIngber, Donald


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