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dc.contributor.authorRasmuson, Agnes
dc.contributor.authorKock, Anna
dc.contributor.authorFuskevåg, Ole-Martin
dc.contributor.authorKruspig, Björn
dc.contributor.authorSimon-Santamaria, Jaione
dc.contributor.authorGogvadze, Vladimir
dc.contributor.authorJohnsen, John Inge
dc.contributor.authorKogner, Per
dc.contributor.authorSveinbjørnsson, Baldur
dc.date.accessioned2012-09-10T11:57:49Z
dc.date.available2012-09-10T11:57:49Z
dc.date.issued2012
dc.description.abstractProstaglandin E2 (PGE2) is an important mediator in tumor-promoting inflammation. High expression of cyclooxygenase-2 (COX-2) has been detected in the embryonic childhood tumor neuroblastoma, and treatment with COX inhibitors significantly reduces tumor growth. Here, we have investigated the significance of a high COX-2 expression in neuroblastoma by analysis of PGE2 production, the expression pattern and localization of PGE2 receptors and intracellular signal transduction pathways activated by PGE2. A high expression of the PGE2 receptors, EP1, EP2, EP3 and EP4 in primary neuroblastomas, independent of biological and clinical characteristics, was detected using immunohistochemistry. In addition, mRNA and protein corresponding to each of the receptors were detected in neuroblastoma cell lines. Immunofluorescent staining revealed localization of the receptors to the cellular membrane, in the cytoplasm, and in the nuclear compartment. Neuroblastoma cells produced PGE2 and stimulation of serum-starved neuroblastoma cells with PGE2 increased the intracellular concentration of calcium and cyclic AMP with subsequent phosphorylation of Akt. Addition of 16,16-dimethyl PGE2 (dmPGE2) increased cell viability in a time, dose- and cell line-dependent manner. Treatment of neuroblastoma cells with a COX-2 inhibitor resulted in a diminished cell growth and viability that was reversed by the addition of dmPGE2. Similarly, PGE2 receptor antagonists caused a decrease in neuroblastoma cell viability in a dose-dependent manner. These findings demonstrate that PGE2 acts as an autocrine and/or paracrine survival factor for neuroblastoma cells. Hence, specific targeting of PGE2 signaling provides a novel strategy for the treatment of childhood neuroblastoma through the inhibition of important mediators of tumor-promoting inflammation.en
dc.identifier.citationPLoS ONE (2012), 7(1): e29331en
dc.identifier.cristinIDFRIDAID 892738
dc.identifier.doidoi: 10.1371/journal.pone.0029331
dc.identifier.issn1932-6203
dc.identifier.urihttps://hdl.handle.net/10037/4423
dc.identifier.urnURN:NBN:no-uit_munin_4150
dc.language.isoengen
dc.publisherPublic Library of Science (PLoS)en
dc.rights.accessRightsopenAccess
dc.subjectVDP::Medisinske Fag: 700::Klinisk medisinske fag: 750::Onkologi: 762en
dc.subjectVDP::Medical disciplines: 700::Clinical medical disciplines: 750::Oncology: 762en
dc.titleAutocrine Prostaglandin E-2 Signaling Promotes Tumor Cell Survival and Proliferation in Childhood Neuroblastomaen
dc.typeJournal articleen
dc.typeTidsskriftartikkelen
dc.typePeer revieweden


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