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dc.contributor.authorLeiss, Lina Wiken_US
dc.contributor.authorMutlu, Ercanen_US
dc.contributor.authorØyan, Anne Margreteen_US
dc.contributor.authorYan, Taoen_US
dc.contributor.authorTsinkalovsky, Olegen_US
dc.contributor.authorSleire, Lindaen_US
dc.contributor.authorPetersen, Kjellen_US
dc.contributor.authorRahman, Mohummad Aminuren_US
dc.contributor.authorJohannessen, Mireille Kayitesien_US
dc.contributor.authorMitra, Siddharta S.en_US
dc.contributor.authorJacobsen, Hegeen_US
dc.contributor.authorTalasila, Krishna Mukharjien_US
dc.contributor.authorMiletic, Hrvojeen_US
dc.contributor.authorJonassen, Ingeen_US
dc.contributor.authorLi, Xingangen_US
dc.contributor.authorBrons, Nicolas H.C.en_US
dc.contributor.authorKalland, Karl-Henningen_US
dc.contributor.authorWang, Jianen_US
dc.contributor.authorEnger, Per Øyvinden_US
dc.date.accessioned2018-03-01T13:08:27Z
dc.date.available2018-03-01T13:08:27Z
dc.date.issued2017-02-07
dc.PublishedLeiss LW, Mutlu E, Øyan AM, Yan T, Tsinkalovsky O, Sleire L, Petersen K, Rahman M, Johannessen MK, Mitra SS, Jacobsen H, Talasila KM, Miletic H, Jonassen I, Li X, Brons NH, Kalland K-H, Wang J, Enger PØ. Tumour-associated glial host cells display a stem-like phenotype with a distinct gene expression profile and promote growth of GBM xenografts. BMC Cancer. 2017;17:108eng
dc.identifier.issn1471-2407
dc.identifier.urihttps://hdl.handle.net/1956/17440
dc.description.abstractBackground: Little is known about the role of glial host cells in brain tumours. However, supporting stromal cells have been shown to foster tumour growth in other cancers. Methods: We isolated stromal cells from patient-derived glioblastoma (GBM) xenografts established in GFP-NOD/scid mice. With simultaneous removal of CD11b+ immune and CD31+ endothelial cells by fluorescence activated cell sorting (FACS), we obtained a population of tumour-associated glial cells, TAGs, expressing markers of terminally differentiaed glial cell types or glial progenitors. This cell population was subsequently characterised using gene expression analyses and immunocytochemistry. Furthermore, sphere formation was assessed in vitro and their glioma growth-promoting ability was examined in vivo. Finally, the expression of TAG related markers was validated in human GBMs. Results: TAGs were highly enriched for the expression of glial cell proteins including GFAP and myelin basic protein (MBP), and immature markers such as Nestin and O4. A fraction of TAGs displayed sphere formation in stem cell medium. Moreover, TAGs promoted brain tumour growth in vivo when co-implanted with glioma cells, compared to implanting only glioma cells, or glioma cells and unconditioned glial cells from mice without tumours. Genome-wide microarray analysis of TAGs showed an expression profile distinct from glial cells from healthy mice brains. Notably, TAGs upregulated genes associated with immature cell types and self-renewal, including Pou3f2 and Sox2. In addition, TAGs from highly angiogenic tumours showed upregulation of angiogenic factors, including Vegf and Angiopoietin 2. Immunohistochemistry of three GBMs, two patient biopsies and one GBM xenograft, confirmed that the expression of these genes was mainly confined to TAGs in the tumour bed. Furthermore, their expression profiles displayed a significant overlap with gene clusters defining prognostic subclasses of human GBMs. Conclusions: Our data demonstrate that glial host cells in brain tumours are functionally distinct from glial cells of healthy mice brains. Furthermore, TAGs display a gene expression profile with enrichment for genes related to stem cells, immature cell types and developmental processes. Future studies are needed to delineate the biological mechanisms regulating the brain tumour-host interplay.en_US
dc.language.isoengeng
dc.publisherBioMed Centraleng
dc.rightsAttribution CC BYeng
dc.rights.urihttp://creativecommons.org/licenses/by/4.0eng
dc.subjectGlioblastomaeng
dc.subjectTumour-host interplayeng
dc.subjectTumour-associated glial cellseng
dc.subjectGFF-NOD/scid miceeng
dc.subjectXenograft tumourseng
dc.subjectGene expression analysiseng
dc.subjectStem cell markerseng
dc.subjectPOU3F2eng
dc.titleTumour-associated glial host cells display a stem-like phenotype with a distinct gene expression profile and promote growth of GBM xenograftsen_US
dc.typePeer reviewed
dc.typeJournal article
dc.date.updated2018-01-03T17:48:13Z
dc.description.versionpublishedVersionen_US
dc.rights.holderCopyright 2017 The Author(s)
dc.identifier.doihttps://doi.org/10.1186/s12885-017-3109-8
dc.identifier.cristin1472333
dc.source.journalBMC Cancer


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