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dc.contributor.authorKundu, Somduttaen_US
dc.date.accessioned2018-08-02T12:03:42Z
dc.date.available2018-08-02T12:03:42Z
dc.date.issued2018-06-29
dc.date.submitted2018-06-28T22:00:11Z
dc.identifier.urihttps://hdl.handle.net/1956/17969
dc.description.abstractGlioblastomas (GBM), a grade IV astrocytoma, is the most common and aggressive primary brain tumors in adults, associated with short survival and uniformly fatal outcome irrespective of treatment. GBM is highly heterogeneous at both molecular and histological levels, including pseudopalisading necrosis, that make GBM most hypoxic and angiogenic tumor in nature. Recent transcriptomic profiling has identified 4 distinct subtypes of GBM based on specific gene expression pattern. Of these the mesenchymal GBM subtype was reported to be the most aggressive one with the worst clinical outcome. Caveolin-1 (Cav-1) is well known principle scaffolding protein in caveole that directly interacts with several signalling molecules and play crucial role in numerous signalling pathways. Over the past 10-15 years, Cav-1 has been found to have oncogenic and metastasis promoting roles in many aspects depending on the tumour type or tissue of interest. Within our project we investigated the role of a hypoxic microenvironment on Cav-1 expression and on mesenchymal and proneural markers by western blotting. Our preliminary data indicate that Cav-1 is elevated under hypoxia in a fraction of GBM cell lines. Upregulation of Cav-1 was confirmed in GBM patient samples around necrotic areas, however, expression pattern of Cav-1 showed inter- and intra-tumoral heterogeneity. Despite the heterogeneity, Cav-1 expression was found to be highly upregulated in hypoxic regions in most of GBM samples, indicating a possible connection between hypoxia and Cav-1 expression. TCGA patient data indicated a correlation of Cav-1 with mesenchymal markers and anti-correlation with proneural markers. Thus, we further investigated whether hypoxia induced a proneural to mesenchymal switch in GBM cell lines. Proneural markers PDGFRA and olig2 were downregulated under hypoxia, however no clear pattern for the mesenchymal markers YKL40, pSTAT3 and CD44 was observed. In conclusion, our results show that Cav-1 is upregulated under hypoxia in a subset of GBM, which parallels downregulation of proneural markers. Whether a mesenchymal shift is induced under hypoxia and whether this might be dependent on Cav-1 needs to be elucidated in future studies.en_US
dc.language.isoengeng
dc.publisherThe University of Bergeneng
dc.subjectGlioblastomaeng
dc.subjectGBM subtypeseng
dc.subjectCancer steam celleng
dc.subjectTumour microenvironmenteng
dc.subjectHypoxiaeng
dc.subjectEMTeng
dc.subjectCaveolin-1eng
dc.subjectHIF-1Aeng
dc.subjectTherapeutic treatmenteng
dc.subjectMesenchymal subtypeeng
dc.subjectCancereng
dc.subjectBiomedicineeng
dc.subjectBiomedisineng
dc.subject.meshGlioblastomaeng
dc.subject.meshHypoxiaeng
dc.subject.meshMesenchymal Stromal Cellseng
dc.subject.meshCaveolin 1eng
dc.titleRole of Caveolin-1 in Hypoxia and Proneural to Mesenchymal Transition of Glioblastomaen_US
dc.typeMaster thesis
dc.date.updated2018-06-28T22:00:11Z
dc.rights.holderCopyright the Author. All rights reserved
dc.description.degreeMaster's Thesis in Biomedical Sciences
dc.description.localcodeMAMD-MEDBI
dc.description.localcodeBMED395
dc.subject.nus751910eng
dc.subject.nsiVDP::Medisinske Fag: 700::Basale medisinske, odontologiske og veterinærmedisinske fag: 710::Medisinsk biokjemi: 726en_US
fs.subjectcodeBMED395
fs.unitcode13-14-0


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