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dc.contributor.authorTümmler, Conny
dc.contributor.authorSnapkov, Igor
dc.contributor.authorWickström, Malin
dc.contributor.authorMoens, Ugo
dc.contributor.authorLjungblad, Linda
dc.contributor.authorElfman, Maria
dc.contributor.authorWinberg, Jan-Olof
dc.contributor.authorKogner, Per
dc.contributor.authorJohnsen, John Inge
dc.contributor.authorSveinbjørnsson, Baldur
dc.date.accessioned2018-06-21T07:34:16Z
dc.date.available2018-06-21T07:34:16Z
dc.date.issued2017-07-27
dc.description.abstractPro-inflammatory cells, cytokines, and chemokines are essential in promoting a tumor supporting microenvironment. Chemerin is a chemotactic protein and a natural ligand for the receptors CMKLR1, GPR1, and CCRL2. The chemerin/CMKLR1 axis is involved in immunity and inflammation, and it has also been implicated in obesity and cancer.<p> In neuroblastoma, a childhood tumor of the peripheral nervous system we identified correlations between high CMKLR1 and GPR1 expression and reduced overall survival probability. CMKLR1, GPR1, and chemerin RNA and protein were detected in neuroblastoma cell lines and neuroblastoma primary tumor tissue. Chemerin induced calcium mobilization, increased MMP-2 synthesis as well as MAP-kinase- and Akt-mediated signaling in neuroblastoma cells. Stimulation of neuroblastoma cells with serum, TNFα or IL-1β increased chemerin secretion. The small molecule CMKLR1 antagonist α-NETA reduced the clonogenicity and viability of neuroblastoma cell lines indicating the chemerin/CMKLR1 axis as a promoting factor in neuroblastoma tumorigenesis. Furthermore, nude mice carrying neuroblastoma SK-N-AS cells as xenografts showed impaired tumor growth when treated daily with α-NETA from day 1 after tumor cell injection.<p> This study demonstrates the potential of the chemerin/CMKLR1 axis as a prognostic factor and possible therapeutic target in neuroblastoma.en_US
dc.description.sponsorshipUiT - The Arctic University of Norway Northern Regional Health Authority Erna and Olav Aakre Foundation for Cancer Research The Swedish Children's Cancer Foundation Swedish Foundation for Strategic Research Swedish Cancer Society Swedish Research Councilen_US
dc.descriptionSource at <a href=https://doi.org/10.18632/oncotarget.19619> https://doi.org/10.18632/oncotarget.19619 </a>.en_US
dc.identifier.citationTümmler, C., Snapkov, I.S., Wickström, M., Moens, U., Ljungblad, L., Elfman, L., ... Sveinbjørnsson, B. (2017). Inhibition of chemerin/CMKLR1 axis in neuroblastoma cells reduces clonogenicity and cell viability in vitro and impairs tumor growth in vivo. OncoTarget, 8(56), 95135-95151.en_US
dc.identifier.cristinIDFRIDAID 1531858
dc.identifier.doi10.18632/oncotarget.19619
dc.identifier.issn1949-2553
dc.identifier.urihttps://hdl.handle.net/10037/12937
dc.language.isoengen_US
dc.publisherImpact Journalsen_US
dc.relation.ispartofTümmler, C. (2019). Novel Inflammatory Mediators in Neuroblastoma Tumorigenesis. (Doctoral thesis). <a href=https://hdl.handle.net/10037/17068>https://hdl.handle.net/10037/17068</a>.
dc.relation.journalOncoTarget
dc.rights.accessRightsopenAccessen_US
dc.subjectpediatric canceren_US
dc.subjectneuroblastomaen_US
dc.subjectinflammationen_US
dc.subjectGPCRen_US
dc.subjectchemerinen_US
dc.subjectVDP::Medisinske Fag: 700::Helsefag: 800en_US
dc.subjectVDP::Medical disciplines: 700::Health sciences: 800en_US
dc.titleInhibition of chemerin/CMKLR1 axis in neuroblastoma cells reduces clonogenicity and cell viability in vitro and impairs tumor growth in vivoen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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