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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.identifier.citationScientific Reports. 2020, 10en_US
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.publisherSpringer Natureen_US
dc.rightsNavngivelse 4.0 Internasjonal*
dc.titleNephronectin promotes breast cancer brain metastatic colonization via its integrin-binding domainsen_US
dc.typePeer revieweden_US
dc.typeJournal articleen_US
dc.source.journalScientific Reportsen_US
dc.description.localcodeOpen Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit

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