Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Expression data from Versican (VCAN) protein treated ovarian cancer cell line OVCA433

ABSTRACT: Advanced ovarian cancer is the most lethal gynecologic malignancy in the United States. Currently patients are treated by surgical cytoreductive surgery with the aim of reducing tumor burden to microscopic disease followed by adjuvant combined treatment with a platinum and taxane containing chemotherapy, which affords 80% of patients an initial complete response. However, Abdominal and pelvic recurrence rates are high and response to further chemotherapy is limited. Attempts at introducing biologic therapeutic agents to improve outcome in this disease are ongoing, while prognostic or predictive biomarkers that can stratify patients for treatment are still lacking. Using transcriptome profiling of microdissected tissue samples from high-grade serous ovarian cancer patients, we identified a cancer associated fibroblast (CAF) specific gene signature. Versican, which encodes a extracellular matrix protein, was one of the identified genes which demonstrated up-regulation in cancer stroma. To investigate the function roles, signaling machanism and the effect of versican treatment on ovarian cancer cells, transcriptome profiling of versican treated OVCA433 high-grade serous ovarian cancer cells was performed. High grade serous ovarian cancer cell line OVCA433 was used. Total RNA was isolated from control samples and versican treated cancer cell samples at 48 hours post-treatment followed by cDNA synthesis, IVT and biotin labeling. Samples were then hybridized onto Affymetrix Human genome U133 plus 2.0 microarrays. For each treatment group, three independent samples were prepared for the microarray experiment.

ORGANISM(S): Homo sapiens

SUBMITTER: Tsz-Lun Yeung

PROVIDER: E-GEOD-40241 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

TGF-β modulates ovarian cancer invasion by upregulating CAF-derived versican in the tumor microenvironment.

Yeung Tsz-Lun TL Leung Cecilia S CS Wong Kwong-Kwok KK Samimi Goli G Thompson Melissa S MS Liu Jinsong J Zaid Tarrik M TM Ghosh Sue S Birrer Michael J MJ Mok Samuel C SC

Cancer research 20130703 16

TGF-β has limited effects on ovarian cancer cells, but its contributions to ovarian tumor growth might be mediated through elements of the tumor microenvironment. In the present study, we tested the hypothesis that TGF modulates ovarian cancer progression by modulating the contribution of cancer-associated fibroblasts (CAF) that are present in the microenvironment. Transcriptome profiling of microdissected stromal and epithelial components of high-grade serous ovarian tumors and TGF-β-treated no ...[more]

PMID: 23824740

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Project description:Advanced ovarian cancer is the most lethal gynecologic malignancy in the United States. Currently patients are treated by surgical cytoreductive surgery with the aim of reducing tumor burden to microscopic disease followed by adjuvant combined treatment with a platinum and taxane containing chemotherapy, which affords 80% of patients an initial complete response. However, Abdominal and pelvic recurrence rates are high and response to further chemotherapy is limited. Attempts at introducing biologic therapeutic agents to improve outcome in this disease are ongoing, while prognostic or predictive biomarkers that can stratify patients for treatment are still lacking. Using a 60-mer 22K oligonucleotide-based array comparative genome hybridization (CGH) platform combined with DNA isolated from microdissected tumor tissue samples, Birrer et. al. reported that the amplification of 5q31-35.3 in ovarian cancer cells is a negative prognostic indicator for patients with advanced stage high-grade serous ovarian cancer (HGSC). Further studies showed that fibroblast growth factor 1 (FGF1) located in the amplicon, may be one of the driving genes for ovarian cancer progression (Birrer et. al., 2007). Besides FGF1, located on the same amplicon is one of its receptors fibroblast growth factor receptor 4 (FGFR4), suggesting that it may also be amplified and may be another driving gene involved in ovarian cancer pathogenesis.In this study, we used microarrays to explore and compare gene expression profiles between FGFR4 knock down ovarian cancer cell lines and their corresponding parental cell lines. Two high grade serous ovarian cancer cell lines: SKOV3 and OVCA432 were selected for this study. For each of the cell lines, two different siRNA sequences which both target human FGFR4 were used. While a non-target scramble siRNA sequence was used as control. Ovarian cancer cells were transfected with siRNA using lipofectamine (Invitrogen). RNA extraction was performed 72 hours post-transfection, followed by hybridization on Affymetrix microarrays.

Project description:Ovarian cancer is the fifth most common form of cancer in women in the United States. Among different types of ovarian cancer, epithelial ovarian cancer is the most common and is highly lethal, however, prognostic and predictive markers, which can be used to predict chemoresponse and patient survival, have not been thoroughly explored. One critically important yet often overlooked component to the tumor progression process is the tumor microenvironment. Primarily composed of fibroblasts and extracellular matrix proteins (ECM) as well as endothelial cells and lymphocytic infiltrate, the tumor microenvironment has been shown to directly affect cell growth, migration, and differentiation through secreted proteins, cell-cell interactions and matrix remodeling (Tlsty and Coussens, 2006). The tumor microenvironment has the potential to promote tumor initiation of normal epithelial cells and facilitate progression of malignant cells, thereby, presenting a unique approach to diagnosing, understanding and treating cancer. Using a whole-genome oligonucleotide array platform to perform transcriptome profiling on the fibroblastic stromal component microdissected from a series of advanced stage high-grade serous ovarian adenocarcinomas, we identified a transcriptome signature for the ovarian cancer associated fibroblast (CAF). We further functionally characterized one of the identified genes, MFAP5, and we showed that stromal MFAP5 is a prognostic marker associated with poor patient survival. In addition to that, to investigate the signaling machanism and the effect of MFAP5 treatment on ovarian cancer cells, transcriptome profiling of MFAP5 treated OVCA432 high-grade serous ovarian cancer cells was performed. Further functional studies showed that stromal MFAP5 modulated ovarian cancer cell motility and invasion potential. High grade serous ovarian cancer cell line OVCA432 was used. Total RNA was isolated from control samples and MFAP5 treated cancer cell samples at 48 hours post-treatment. Followed by cDNA synthesis, IVT and biotin labeling, samples were then hybridized onto Affymetrix Human genome U133 plus 2.0 microarrays. For each treatment group, three independent samples were prepared for the microarray experiment.

Dataset Information

Expression data from Versican (VCAN) protein treated ovarian cancer cell line OVCA433

Publications

TGF-β modulates ovarian cancer invasion by upregulating CAF-derived versican in the tumor microenvironment.

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