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Association of Notch-1, osteopontin and stem-like cells in ENUglioma malignant process

dc.contributor.authorBulnes S.
dc.contributor.authorBermúdez G.
dc.contributor.authorLafuente J.V.
dc.date.accessioned2020-09-02T22:13:34Z
dc.date.available2020-09-02T22:13:34Z
dc.date.issued2018
dc.identifier10.18632/oncotarget.25808
dc.identifier.citation9, 59, 31330-31341
dc.identifier.issn19492553
dc.identifier.urihttps://hdl.handle.net/20.500.12728/3799
dc.descriptionNotch-1 and osteopontin (OPN) mediate angiogenesis and glioma stem-like cell (GSLC) maintenance. However, the relationship between these molecules and GSLCs during the development of glioma is unknown. We investigate the expression of Notch-1, OPN and vascular endothelial growth factor (VEGF) associated to the stemness markers nestin and CD133 in three stages of murine gliomas induced by N-ethyl-N-nitrosourea (ENU). Notch-1 and OPN overexpress in the intermediate stage (II), which corresponds to the "angiogenesis switch". Nestin+ cells appear in all stages of ENU-glioma but CD133 only from stage II on. In stage III, neoplastic cells expressing nestin, CD133 and nestin/CD133 reside in spheroid-like aggregates (SAs) and in the neoangiogenic border. These aggregates show Notch-1 and VEGF+ surrounding cells and a significant size and density increase with respect to stage I (3.3 ± 1.5 to 22.4 ± 6.3 μm2, no = 0.3 ± 0.1 to 4.2 ± 0.9, from stage I to stage III, respectively). OPN expression increases in correlation to the glioma malignancy from 4.5 ± 1.8% (I) to 12.3 ± 1.2% of OPN+ cells (III). It predominates in astrocyte-like cells of the neoangiogenic border, displaying co-location with VEGF and CD133. The OPN immunopositivity distribution correlates with the CD133 distribution. In conclusion, OPN co-expressing with CD133 contributes to the identification of GSLCs in the neoangiogenic border, while Notch-1 is present around SAs in advanced stages. The ENU-glioma, mainly in stage II, is a useful tool for assessing new antitumour therapies against these molecules. © Bulnes et al.
dc.language.isoen
dc.publisherImpact Journals LLC
dc.subjectAngiogenesis
dc.subjectGlioma stem-like cells
dc.subjectN-ethyl-N-nitrosourea
dc.subjectNotch-1
dc.subjectOsteopontin
dc.subjectCD133 antigen
dc.subjectethylnitrosourea
dc.subjectnestin
dc.subjectNotch1 receptor
dc.subjectosteopontin
dc.subjectvasculotropin
dc.subjectadult
dc.subjectanimal cell
dc.subjectanimal experiment
dc.subjectanimal model
dc.subjectanimal tissue
dc.subjectArticle
dc.subjectastrocyte
dc.subjectcancer staging
dc.subjectcell aggregation
dc.subjectcell density
dc.subjectcell size
dc.subjectdisease course
dc.subjectglioma cell
dc.subjectglioma stem cell
dc.subjectmouse
dc.subjectnonhuman
dc.subjectprotein expression
dc.subjectprotein localization
dc.subjectspheroid cell
dc.subjecttumor vascularization
dc.titleAssociation of Notch-1, osteopontin and stem-like cells in ENUglioma malignant process
dc.typeArticle


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