Transcriptomics

Dataset Information

14

Hypoxia-responsive gene expression profile of U87 MG glioblastoma cells and their exosomes.


ABSTRACT: How cancer cells adapt to hypoxia during tumor development remains an important question. The hypothesis tested in the present study was that tumor cell-derived exosome vesicles (also known as microvesicles or extracellular vesicles) are mediators of hypoxia-dependent intercellular signaling in glioblastoma (GBM), i.e. highly aggressive brain tumors characterized by hypoxia and a vascular density that is among the highest of all human malignancies. In vitro hypoxia experiments and studies with patient materials reveal the enrichment in exosomes of hypoxia-regulated mRNAs and proteins, several of which were associated with poor patient prognosis. We show that cancer cell exosomes mediate hypoxia-dependent, phenotypic modulation of stromal cells in vitro and ex vivo, resulting in accelerated GBM tumor angiogenesis and growth in mice. These data suggest that exosomes constitute potent mediators of hypoxia-driven tumor development, and circulating multiparameter biomarkers of tumor hypoxia. U87 MG glioblastoma cells were grown at normoxic (21% oxygen) or hypoxic (1% oxygen) conditions for 48 hours. Conditioned media from normoxic and hypoxic cells were then used to isolate exosomes by differential centrifugation. Both cells and exosomes were lysed in Trizol reagent, and RNA was isolated.Total RNA from all samples (four types of samples in three biological repilicates) was subjected to genome-wide transcriptional analysis with Illumina HumanHT-12 V3.0 expression beadchip. Gene expression profile obtained from hypoxic U87 MG glioblastoma cells was compared to the profile of normoxic control cells. Analogically, gene expression profile obtained from hypoxic U87 MG cells was compared to the profile of exosomes secreted by normoxic U87 MG cells.

ORGANISM(S): Homo sapiens  

SUBMITTER: H C Christianson   M Ringnér  E Bourseau-Guilmain  J E Welch  M Mörgelin  M Belting  J Bengzon  Paulina Kucharzewska  E Fredlund  K J Svensson  P Kucharzewska 

PROVIDER: E-GEOD-45301 | ArrayExpress | 2013-03-20

SECONDARY ACCESSION(S): GSE45301PRJNA193437

REPOSITORIES: GEO, ArrayExpress

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Publications

BASE--2nd generation software for microarray data management and analysis.

Vallon-Christersson Johan J   Nordborg Nicklas N   Svensson Martin M   Häkkinen Jari J  

BMC Bioinformatics 20091012


BACKGROUND: Microarray experiments are increasing in size and samples are collected asynchronously over long time. Available data are re-analysed as more samples are hybridized. Systematic use of collected data requires tracking of biomaterials, array information, raw data, and assembly of annotations. To meet the information tracking and data analysis challenges in microarray experiments we reimplemented and improved BASE version 1.2. RESULTS: The new BASE presented in this report is a comprehe  ...[more]

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