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dc.contributor.authorNorvoll Magnussen, Synnøve
dc.contributor.authorToraskar, Jimita Prashant
dc.contributor.authorWilhelm, Imola
dc.contributor.authorHasko, Janos
dc.contributor.authorFigenschau, Stine
dc.contributor.authorMolnar, Judit
dc.contributor.authorSeppola, Marit
dc.contributor.authorSteigen, Sonja Eriksson
dc.contributor.authorSteigedal, Tonje S.
dc.contributor.authorHadler-Olsen, Elin Synnøve
dc.contributor.authorKrizbai, Istvan
dc.contributor.authorSvineng, Gunbjørg
dc.date.accessioned2020-08-04T08:38:58Z
dc.date.available2020-08-04T08:38:58Z
dc.date.issued2020-07-22
dc.description.abstractThis study demonstrates a role for the extracellular matrix protein nephronectin (NPNT) in promoting experimental breast cancer brain metastasis, possibly through enhanced binding to- and migration through brain endothelial cells. With the introduction of more targeted breast cancer treatments, a prolonged survival has resulted during the last decade. Consequently, an increased number of patients develop metastasis in the brain, a challenging organ to treat. We recently reported that NPNT was highly expressed in primary breast cancer and associated with unfavourable prognosis. The current study addresses our hypothesis that NPNT promotes brain metastases through its integrin-binding motifs. SAGE-sequencing revealed that NPNT was significantly up-regulated in human breast cancer tissue compared to pair-matched normal breast tissue. Human brain metastatic breast cancers expressed both NPNT and its receptor, integrin α8β1. Using an open access repository; BreastMark, we found a correlation between high NPNT mRNA levels and poor prognosis for patients with the luminal B subtype. The 66cl4 mouse cell line was used for expression of wild-type and mutant NPNT, which is unable to bind α8β1. Using an in vivo model of brain metastatic colonization, 66cl4-NPNT cells showed an increased ability to form metastatic lesions compared to cells with mutant NPNT, possibly through reduced endothelial adhesion and transmigration.en_US
dc.identifier.citationNorvoll Magnussen S, Toraskar JP, Wilhelm I, Hasko J, Figenschau S, Molnar, Seppola M, Steigen SE, Steigedal TS, Hadler-Olsen ES, Krizbai I, Svineng g. Nephronectin promotes breast cancer brain metastatic colonization via its integrin-binding domains. Scientific Reports. 2020en_US
dc.identifier.cristinIDFRIDAID 1821362
dc.identifier.doihttps://doi.org/10.1038/s41598-020-69242-1
dc.identifier.issn2045-2322
dc.identifier.urihttps://hdl.handle.net/10037/18912
dc.language.isoengen_US
dc.publisherSpringer Natureen_US
dc.relation.journalScientific Reports
dc.rights.accessRightsopenAccessen_US
dc.rights.holderCopyright 2020 The Author(s)en_US
dc.subjectVDP::Medical disciplines: 700::Basic medical, dental and veterinary science disciplines: 710en_US
dc.subjectVDP::Medisinske Fag: 700::Basale medisinske, odontologiske og veterinærmedisinske fag: 710en_US
dc.titleNephronectin promotes breast cancer brain metastatic colonization via its integrin-binding domainsen_US
dc.type.versionpublishedVersionen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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