Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Deregulation of PPARβ/δ target genes in tumor-associated macrophages by fatty acid ligands in the ovarian cancer microenvironment - ChIPseq

ABSTRACT: PPARD and RXR genome wide binding in tumor associated macrophages from serous ovarian carcinoma was characterized.

INSTRUMENT(S): Illumina HiSeq 1500

ORGANISM(S): Homo sapiens

SUBMITTER: Florian Finkernagel

PROVIDER: E-MTAB-3166 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Deregulation of PPARβ/δ target genes in tumor-associated macrophages by fatty acid ligands in the ovarian cancer microenvironment.

Schumann Tim T Adhikary Till T Wortmann Annika A Finkernagel Florian F Lieber Sonja S Schnitzer Evelyn E Legrand Nathalie N Schober Yvonne Y Nockher W Andreas WA Toth Philipp M PM Diederich Wibke E WE Nist Andrea A Stiewe Thorsten T Wagner Uwe U Reinartz Silke S Müller-Brüsselbach Sabine S Müller Rolf R

Oncotarget 20150501 15

The nuclear receptor peroxisome proliferator-activated receptor β/δ (PPARβ/δ) is a lipid ligand-inducible transcription factor associated with macrophage polarization. However, its function in tumor-associated macrophages (TAMs) has not been investigated to date. Here, we report the PPARβ/δ-regulated transcriptome and cistrome for TAMs from ovarian carcinoma patients. Comparison with monocyte-derived macrophages shows that the vast majority of direct PPARβ/δ target genes are upregulated in TAMs ...[more]

PMID: 25968567

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Project description:Background: Malignant ascites is often present at diagnostic in women with advanced ovarian cancer (OC) and its presence is associated with a worse outcome. Human peritoneal mesothelial cells (HPMCs) are key components of malignant ascites. Although the interplay between HPMCs and OC cells is believed to be critical for tumor progression, it has not been well characterized. The purpose of this study was to assess the effect of ascites on HPMCs and clarify the role of HPMCs in OC progression. Methods: Human OC ascites and benign peritoneal fluids were assessed for their ability to stimulate HPMC proliferation. Conditioned medium from ascites- and benign fluid-stimulated HPMCs were compared for their ability to attenuate apoptosis induced by TNF-related apoptosis-inducing ligand (TRAIL). We conducted a comparative analysis of global expression changes in ascites-stimulated HPMCs using Agilent oligonucleotide microarrays. Results: As compared to benign peritoneal fluids, malignant ascites stimulated the proliferation of HPMCs. TRAIL-induced apoptosis was attenuated in OC cells exposed to conditioned medium from ascites-stimulated HPMCs as compared to OC cells exposed to conditioned medium from benign fluid-stimulated HPMCs. A total of 649 genes were differentially expressed in ascites-stimulated HPMCs. Based on a ratio of more than 1.5-fold and a P < 0.05, 484 genes were up-regulated and 165 genes were down-regulated in ascites-exposed HPMCs. Stimulation of HPMCs with OC ascites resulted in differential expression of genes mainly associated with the regulation of cell growth and proliferation, cell death, cell cycle and cell assembly and organization, compared to benign peritoneal fluids. Top networks up-regulated by OC ascites included Akt and NF-M-NM-:B survival pathways whereas vascular endothelial growth factor (VEGF) pathway was down-regulated. Conclusions: The results of this study not only provide evidence supporting the importance of the interplay between cancer cells and HPMCs but also define the role that the tumor environment plays in these interactions. The expression profiles from human peritoneal mesothelial cells (HPMC) cultures exposed to peritoneal fluids and ovarian cancer ascites were compared using the Agilent Whole Human Genome Oligonucleotide microarrays, containing 44,000 genes. Microarrays were performed on HPMCs exposed to 3 malignant ascites from women with advanced (stage III/IV) serous OC and two benign peritoneal fluids. First, we generated lists of significantly up-regulated and down-regulated genes that were differentially expressed between OC ascites (OVC346, OVC508 and OVC509) and control OV370 peritoneal fluid. Then, the set of genes that were commonly expressed between control peritoneal fluids (OV370 and OV401) were subtracted from the first list of genes to generate a dataset of differentially expressed genes between malignant ascites and benign peritoneal fluids.

Dataset Information

Deregulation of PPARβ/δ target genes in tumor-associated macrophages by fatty acid ligands in the ovarian cancer microenvironment - ChIPseq

Publications

Deregulation of PPARβ/δ target genes in tumor-associated macrophages by fatty acid ligands in the ovarian cancer microenvironment.

Similar Datasets

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