Unknown,Transcriptomics,Genomics,Proteomics

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Collagen induces maturation of human monocyte-derived dendritic cells by signalling through Osteoclast Associated Receptor

ABSTRACT: Human immature dendritic cells derived from monocytes were activated to become mature dendritic cells by exposure to platebound Collagen I or Collagen. The importance of OSCAR-signalling was evaluated by pre-incubating the immature dendritic cells with an inhibitory monoclonal antibody to the OSCAR receptor, or an isotype control. As a positive control, immature dendritic cells were activated by using LPS. The set-up was examined at 4 hours and 20 hours to evaluate early and late effects of OSCAR signalling.

INSTRUMENT(S): NanoDrop® ND-1000 (Saveen&Werner)., Affymetix Gene Titan, Affymetrix Gene Titan, Agilent 2100 Bioanalyser, RNA 6000 Nano Kit chips (Agilent Technologies). NanoDrop® ND-1000 (Saveen&Werner).

ORGANISM(S): Homo sapiens

SUBMITTER: Pernille Keller

PROVIDER: E-MTAB-2904 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Objectives and goals: The causes and molecular pathology of ovarian cancer are essentially unknown. However, it is generally understood that serous ovarian borderline tumors (SBOT) and well differentiated (WD) serous ovarian carcinomas (SC) have a similar tumorigenetic pathway, distinct from moderately (MD) and poorly differentiated (PD) SC. The aim of this study was to identify mRNAs differentially expressed between MD/PD SC, SBOT and superficial scrapings from normal ovaries (SNO),and to correlate these mRNAs with clinical parameters. Results: From the global gene expression analyses, thirty mRNAs differentially expressed between MD/PD SC, SBOT and SNO were selected and validated by RT-qPCR, verifying 21 mRNAs to be significantly differentially expressed (p<0.01). Of these, 13 mRNAs were differentially expressed in MD/PD SC compared with SNO (p<0.01) and were correlated with clinical parameters. VEGFA was significantly upregulated (FC=6.1, p=6.0x10-6), and correlated with progression-free survival (p=0.037). ZNF385B was significantly downregulated (FC=-130.5, p=1.2x10-7), and correlated with overall survival (p=0.03). An increased TPX2 (p=0.03) and FOXM1 (p=0.044) expression correlated with optimal normalization of serum CA125 after treatment. Furthermore, we present a common molecular pathway for MD/PD SC, including VEGFA, FOXM1, TPX2, BIRC5 and TOP2A, all significantly upregulated and interacting with TP53. Conclusions: We have identified 21 mRNAs differentially expressed (p<0.01) between MD/PD SC, SBOT and SNO. Thirteen were differentially expressed in MD/PD SC, including VEGFA and ZNF385B, correlating with survival, and FOXM1 and TPX2, correlating with normalization of serum CA125. By the use of oligonucleotid microarrays (Affymetrix U133 Plus 2.0 Arrays) differences in mRNA expression between eleven MD/PD SC, eight SBOT and four SNO samples were analyzed. Differentially expressed mRNAs were selected for validation by RT-qPCR in additional samples totaling 21 MD/PD SC, 13 SBOT and seven samples of SNO. Each mRNA was run in quadruple. The mRNAs differentially expressed in MD/PD SC compared with SNO were correlated with clinical parameters.

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Collagen induces maturation of human monocyte-derived dendritic cells by signalling through Osteoclast Associated Receptor

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