{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,26]],"date-time":"2025-10-26T21:37:41Z","timestamp":1761514661826,"version":"3.37.3"},"reference-count":54,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2020,10,17]],"date-time":"2020-10-17T00:00:00Z","timestamp":1602892800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"German Cancer Aid Society"},{"DOI":"10.13039\/501100005972","name":"Deutsche Krebshilfe","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005972","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Deutsche Forschungsgesellschaft"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,4,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Chronic inflammation induces Barrett\u2019s Esophagus (BE) which can advance to esophageal adenocarcinoma. Elevated levels of interleukin (IL)-1b, IL-6 and IL-8 together with activated nuclear factor-kappaB (NF-\u03baB), have been identified as important mediators of tumorigenesis. The inflammatory milieu apart from cancer cells and infiltrating immune cells contains myofibroblasts (MFs) that express aSMA and Vimentin. As we observed that increased NF-\u03baB activation and inflammation correlates with increased MF recruitment and an accelerated phenotype we here analyze the role of NF-\u03baB in MF during esophageal carcinogenesis in our L2-IL-1B mouse model. To analyze the effect of NF-\u03baB signaling in MFs, we crossed L2-IL-1B mice to tamoxifen inducible Vim-Cre (Vim-CreTm) mice and floxed RelA (p65fl\/fl) mice to specifically eliminate NF-\u03baB signaling in MF (IL-1b.Vim-CreTm.p65fl\/fl). The interaction of epithelial cells and stromal cells was further analyzed in mouse BE organoids and patient-derived human organoids. Histological scoring of IL-1b.Vim-CreTm.p65fl\/fl mice showed a significantly attenuated phenotype compared with L2-IL-1B mice, with mild inflammation, decreased metaplasia and no dysplasia. This correlated with decreased proliferation and increased differentiation in cardia tissue of IL-1b.Vim-CreTm.p65fl\/fl compared with L2-IL-1B mice. Distinct changes of cytokines and chemokines within the local microenvironment in IL-1b.Vim-CreTm.p65fl\/fl mice reflected the histopathological abrogated phenotype. Co-cultured NF-\u03baB inhibitor treated MF with mouse BE organoids demonstrated NF-\u03baB-dependent growth and migration. MFs are essential to form an inflammatory and procarcinogenic microenvironment and NF-\u03baB signaling in stromal cells emerges as an important driver of esophageal carcinogenesis. Our data suggest anti-inflammatory approaches as preventive strategies during surveillance of BE patients.<\/jats:p>","DOI":"10.1093\/carcin\/bgaa109","type":"journal-article","created":{"date-parts":[[2020,10,13]],"date-time":"2020-10-13T19:29:33Z","timestamp":1602617373000},"page":"405-413","source":"Crossref","is-referenced-by-count":10,"title":["Elimination of NF-\u03baB signaling in Vimentin+ stromal cells attenuates tumorigenesis in a mouse model of Barrett\u2019s Esophagus"],"prefix":"10.1093","volume":"42","author":[{"given":"Akanksha","family":"Anand","sequence":"first","affiliation":[{"name":"Department of Medicine II, Klinikum rechts der Isar, Technical University Munich (TUM), M\u00fcnchen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hsin-Yu","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Medicine II, Klinikum rechts der Isar, Technical University Munich (TUM), M\u00fcnchen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Donja","family":"Mohammad-Shahi","sequence":"additional","affiliation":[{"name":"Department of Medicine II, Klinikum rechts der Isar, Technical University Munich (TUM), M\u00fcnchen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonas","family":"Ingermann","sequence":"additional","affiliation":[{"name":"Department of Medicine II, Klinikum rechts der Isar, Technical University Munich (TUM), M\u00fcnchen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Theresa","family":"Baumeister","sequence":"additional","affiliation":[{"name":"Department of Medicine II, Klinikum rechts der Isar, Technical University Munich (TUM), M\u00fcnchen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julia","family":"Strangmann","sequence":"additional","affiliation":[{"name":"Department of Medicine II, Klinikum rechts der Isar, Technical University Munich (TUM), M\u00fcnchen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roland M","family":"Schmid","sequence":"additional","affiliation":[{"name":"Department of Medicine II, Klinikum rechts der Isar, Technical University Munich (TUM), M\u00fcnchen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Timothy C","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Medicine, Columbia University Irving Medical Center, New York, NY, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Quante","sequence":"additional","affiliation":[{"name":"Department of Medicine II, Klinikum rechts der Isar, Technical University Munich (TUM), M\u00fcnchen, Germany"},{"name":"Universit\u00e4tsklinikum Freiburg, Klinik f\u00fcr Innere Medizin II, Hugstetter Stra\u00dfe 55, Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2020,10,17]]},"reference":[{"key":"2021041713561284700_CIT0001","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1053\/j.gastro.2017.09.046","article-title":"Insights into the pathophysiology of esophageal adenocarcinoma","volume":"154","author":"Quante","year":"2018","journal-title":"Gastroenterology"},{"key":"2021041713561284700_CIT0002","doi-asserted-by":"crossref","first-page":"1184","DOI":"10.1093\/jnci\/djn211","article-title":"Incidence of adenocarcinoma of the esophagus among white Americans by sex, stage, and age","volume":"100","author":"Brown","year":"2008","journal-title":"J. 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