Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Regulation of gene expressions in vivo by anti-VEGF and anti-Notch therapy [HG-U133_Plus_2]

ABSTRACT: U87-EV human glioblastoma xenograft tumours is therapeutically treated by bevacizumab, a humanized anti-human VEGF mAb, or dibenzazepine (DBZ), when tumour is established in BALB/c SCID mice. At the end point, collect tumour samples and extracted total RNA for microarray to investigate the gene profile changes compared to control. These include the genes from human tumour cells and mouse host stroma cells. 3 control samples, 3 dibenzazepine-treated samples, 3 bevacizumab-treated samples

ORGANISM(S): Homo sapiens

SUBMITTER: Francesca Buffa

PROVIDER: E-GEOD-39223 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

A core human primary tumor angiogenesis signature identifies the endothelial orphan receptor ELTD1 as a key regulator of angiogenesis.

Masiero Massimo M Simões Filipa Costa FC Han Hee Dong HD Snell Cameron C Peterkin Tessa T Bridges Esther E Mangala Lingegowda S LS Wu Sherry Yen-Yao SY Pradeep Sunila S Li Demin D Han Cheng C Dalton Heather H Lopez-Berestein Gabriel G Tuynman Jurriaan B JB Mortensen Neil N Li Ji-Liang JL Patient Roger R Sood Anil K AK Banham Alison H AH Harris Adrian L AL Buffa Francesca M FM

Cancer cell 20130718 2

Limited clinical benefits derived from anti-VEGF therapy have driven the identification of new targets involved in tumor angiogenesis. Here, we report an integrative meta-analysis to define the transcriptional program underlying angiogenesis in human cancer. This approach identified ELTD1, an orphan G-protein-coupled receptor whose expression is induced by VEGF/bFGF and repressed by DLL4 signaling. Extensive analysis of multiple cancer types demonstrates significant upregulation of ELTD1 in tumo ...[more]

PMID: 23871637

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Project description:Bevacizumab induces glioblastoma resistance in two in vivo xenograft models. Two cell lines were developed with acquired resistance to bevacizumab. Gene expression difference were analyzed between treated and untreated tumors. Purpose: Antiangiogenic therapy reduces vascular permeability and delays progression but may ultimately promote an aggressive treatment-resistant phenotype. The aim of the present study was to identify mechanisms responsible for glioblastoma resistance to antiangiogenic therapy. Experimental Design: Glioma stem cell (GSC) NSC11 and U87 cell lines with acquired resistance to bevacizumab were developed from orthotopic xenografts in nude mice treated with bevacizumab. Genome-wide analyses were used to identify changes in tumor subtype and specific factors associated with resistance. Results: Mice with established parental NSC11 and U87 cells responded to bevacizumab, whereas glioma cell lines derived at the time of acquired resistance to anti-VEGF therapy were resistant to bevacizumab and did not have prolongation of survival compared to untreated controls. Gene expression profiling comparing anti-VEGF therapy-resistant cell lines to untreated controls demonstrated an increase in genes associated with a mesenchymal origin, cellular migration/invasion, and inflammation. Gene Set Enrichment Analysis (GSEA) demonstrated that bevacizumab-treated tumors showed a highly significant correlation to published mesenchymal gene signatures. Mice bearing resistant tumors showed significantly greater infiltration of myeloid cells in NSC11 and U87 resistant tumors. Invasion-related genes were also upregulated in both NSC11 and U87 resistant cells, which had higher invasion rates in vitro compared with their respective parental cell lines. Conclusions: Our studies identify multiple pro-inflammatory factors associated with resistance and identify a proneural-to-mesenchymal transition (PMT) in tumors resistant to antiangiogenic therapy. Glioma cell lines were injected into the caudate of nude mice and were allowed to grow untreated (samples labeled control) or were treated with 10 mg/kg IP twice weekly with bevacizumab (samples labeled Avastin). At the time of animal death, tumor tissue from the mouse was removed, and RNA was isolated and analyzed using gene expression. U87R and NSC11R represent cells resistant to bevacizumab (Avastin).

Dataset Information

Regulation of gene expressions in vivo by anti-VEGF and anti-Notch therapy [HG-U133_Plus_2]

Publications

A core human primary tumor angiogenesis signature identifies the endothelial orphan receptor ELTD1 as a key regulator of angiogenesis.

Similar Datasets

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