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GSE26910
Homo sapiens
21 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Primary tumor growth induces host tissue responses that are believed to support and promote tumor progression. Identification of the molecular characteristics of the tumor microenvironment and elucidation of its crosstalk with tumor cells may therefore be crucial for improving our understanding of the processes implicated in cancer progression, identifying potential therapeutic targets, and uncovering stromal gene expression signatures that may predict clinical outcome. A key issue to resolve, therefore, is whether the stromal response to tumor growth is largely a generic phenomenon, irrespective of the tumor type, or whether the response reflects tumor-specific properties. To address similarity or distinction of stromal gene expression changes during cancer progression, oligonucleotide-based Affymetrix microarray technology was used to compare the transcriptomes of laser-microdissected stromal cells derived from invasive human breast and prostate carcinoma. Invasive breast and prostate cancer-associated stroma was observed to display distinct transcriptomes, with a limited number of shared genes. Interestingly, both breast and prostate tumor-specific dysregulated stromal genes were observed to cluster breast and prostate cancer patients, respectively, into two distinct groups with statistically different clinical outcomes. By contrast, a gene signature that was common to the reactive stroma of both tumor types did not have survival predictive value. Univariate Cox analysis identified genes whose expression level was most strongly associated with patient survival. Taken together, these observations suggest that the tumor microenvironment displays distinct features according to the tumor type that provides survival-predictive value.
Publication Title
Identification of prognostic molecular features in the reactive stroma of human breast and prostate cancer.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Metastasis depends on the ability of tumor cells to establish a relationship with the newly seeded host tissue that is conducive to their survival and proliferation. Recent evidence suggests that tumor cells regulate their own dissemination by preparing permissive metastatic niches within host tissues. However, the factors that are implicated in rendering tissues permissive for metastatic tumor growth have yet to be fully elucidated. Breast tumors arising during pregnancy display highly aggressive behaviour and early metastatic proclivity, raising the possibility that pregnancy may constitute a physiological condition of permissiveness for tumor dissemination. We show that during murine gestation, both the rate and degree of metastatic tumor growth are enhanced irrespective of tumor type and that decreased natural killer (NK) cell activity is responsible for the observed increase in experimental metastasis. We identify gene expression changes in pregnant mouse lung and liver that bear striking similarity with reported pre-metastatic niche signatures and several of the up-regulated genes are indicative of myeloid-cell infiltration. We provide evidence, that CD11b+ Gr-1+ myeloid-derived suppressor cells accumulate in pregnant mice and exert an inhibitory effect on NK cell activity, thereby enhancing metastatic tumor growth. MDSC have never been evoked in the context of pregnancy and our observations suggest that they may represent a further shared mechanism of immune suppression occurring during gestation and tumor growth.
Publication Title
Myeloid-derived suppressor cells are implicated in regulating permissiveness for tumor metastasis during mouse gestation.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina mouse-6 v1.1 expression beadchip
Description
The transcription factor STAT3 is constitutively activated in tumors of different origin but the molecular bases for STAT3 addiction of tumor cells have not yet been clearly identified. We generated knock/in mice carrying the constitutively active Stat3 allele, Stat3C, and showed that Stat3C could enhance Neu oncogenic power, triggering the production of earlier onset, more invasive mammary tumors. Tumor-derived cell lines displayed higher migration and invasion and disrupted distribution of cell-cell junction markers. The tensin family member Cten (C-Terminal Tensin-like), known to mediate EGF-induced migration and highly expressed in inflammatory breast cancer, was up-regulated in both Neu;Stat3C cells and tumors. Both Cten expression and enhanced migration were strictly dependent on Stat3, and Cten silencing normalized cell migration and rescued cell-cell contact defects. Importantly, the pro-inflammatory cytokine IL-6 could mediate Cten induction in MCF10 cells, in an exquisitely Stat3-dependent way. This model allowed us to shed some light on the oncogenic role of Stat3 in the breast, suggesting moreover a mechanism through which inflammatory signals can cooperate with EGF receptors in inflammatory breast cancer.
Publication Title
Constitutively active Stat3 enhances neu-mediated migration and metastasis in mammary tumors via upregulation of Cten.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Cancer stem cells (CSCs) display plasticity and self-renewal properties reminiscent of normal tissue stem cells, but the events responsible for their emergence remain obscure. We recently identified CSCs in Ewing sarcoma family tumors (ESFTs) and showed that they retain mesenchymal stem cell (MSC) plasticity. In the present study, we addressed the mechanisms that underlie ESFT CSC development. We show that the EWS-FLI-1 fusion gene, associated with 85%-90% of ESFTs and believed to initiate their pathogenesis, induces expression of the embryonic stem cell (ESC) genes OCT4, SOX2, and NANOG in human pediatric MSCs (hpMSCs) but not in their adult counterparts. Moreover, under appropriate culture conditions, hpMSCs expressing EWS-FLI-1 generate a cell subpopulation displaying ESFT CSC features in vitro. We further demonstrate that induction of the ESFT CSC phenotype is the result of the combined effect of EWS-FLI-1 on its target gene expression and repression of microRNA-145 (miRNA145) promoter activity. Finally, we provide evidence that EWS-FLI-1 and miRNA-145 function in a mutually repressive feedback loop and identify their common target gene, SOX2, in addition to miRNA145 itself, as key players in ESFT cell differentiation and tumorigenicity. Our observations provide insight for the first time into the mechanisms whereby a single oncogene can reprogram primary cells to display a CSC phenotype.
Publication Title
EWS-FLI-1 modulates miRNA145 and SOX2 expression to initiate mesenchymal stem cell reprogramming toward Ewing sarcoma cancer stem cells.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Expression of the SS18/SYT-SSX fusion protein is believed to underlie the pathogenesis of synovial sarcoma (SS). Recent evidence suggests that deregulation of the Wnt pathway may play an important role in SS but the mechanisms whereby SS18-SSX might affect Wnt signaling remain to be elucidated. Here, we show that SS18/SSX tightly regulates the elevated expression of the key Wnt target AXIN2 in primary SS. SS18-SSX is shown to interact with TCF/LEF, TLE and HDAC but not -catenin in vivo and to induce Wnt target gene expression by forming a complex containing promoter-bound TCF/LEF and HDAC but lacking -catenin. Our observations provide a tumor-specific mechanistic basis for Wnt target gene induction in SS that can occur in the absence of Wnt ligand stimulation.
Publication Title
The fusion protein SS18-SSX1 employs core Wnt pathway transcription factors to induce a partial Wnt signature in synovial sarcoma.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Overexpression of the Polycomb group protein Enhancer of Zeste Homolog 2 (EZH2) occurs in diverse malignancies, including prostate cancer, breast cancer, and glioblastoma multiforme (GBM) (1). Based on its ability to modulate transcription of key genes implicated in cell cycle control, DNA repair and cell differentiation, EZH2 is believed to play a crucial role in tissue-specific stem cell maintenance and tumor development. Here we show that targeted pharmacologic disruption of EZH2 by the S-adenosylhomocysteine hydrolase inhibitor 3-Deazaneplanocin A (DZNep), or its specific down-regulation by shRNA, strongly impairs GBM cancer stem cell self-renewal in vitro and tumor-initiating capacity in vivo. Using genome-wide expression analysis of DZNep-treated GBM cancer stem cells, we found the expression of c-myc, recently reported to be essential for GBM cancer stem cells, to be strongly repressed upon EZH2 depletion. Specific shRNA-mediated down-regulation of EZH2 in combination with chromatin immunoprecipitation (ChIP) experiments revealed that c-myc is a direct target of EZH2 in GBM cancer stem cells. Taken together, our observations provide evidence that direct transcriptional regulation of c-myc by EZH2 may constitute a novel mechanism underlying GBM cancer stem cell maintenance and suggest that EZH2 may be a valuable new therapeutic target for GBM management.
Publication Title
EZH2 is essential for glioblastoma cancer stem cell maintenance.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 2886 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Consider the problem of designing a panel of complex biomarkers to predict a patient's health or disease state when one can pair his or her current test sample, called a target sample, with the patient's previously acquired healthy sample, called a reference sample. As contrasted to a population averaged reference, this reference sample is individualized. Automated predictor algorithms that compare and contrast the paired samples to each other could result in a new generation of test panels that compare to a person's healthy reference to enhance predictive accuracy. This study develops such an individualized predictor and illustrates the added value of including the healthy reference for design of predictive gene expression panels. The objective is to predict each subject's state of infection, e.g., neither exposed nor infected, exposed but not infected, pre-acute phase of infection, acute phase of infection, post-acute phase of infection. Using gene microarray data collected in a large-scale serially sampled respiratory virus challenge study, we quantify the diagnostic advantage of pairing a person's baseline reference with his or her target sample.
Publication Title
An individualized predictor of health and disease using paired reference and target samples.
Sample Metadata Fields
Specimen part, Subject, Time
View Samples- Homo sapiens
- 711 Downloadable Samples
- Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
African-American individuals of the GENOA cohort
Publication Title
Genetic Architecture of Gene Expression in European and African Americans: An eQTL Mapping Study in GENOA.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 97 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [probe set (exon) version (huex10st)
Description
The NIH Roadmap Epigenomics Mapping Consortium aims to produce a public resource of epigenomic maps for stem cells and primary ex vivo tissues selected to represent the normal counterparts of tissues and organ systems frequently involved in human disease.
Publication Title
The NIH Roadmap Epigenomics Mapping Consortium.
Sample Metadata Fields
Sex, Specimen part, Disease, Subject
View Samples- Homo sapiens
- 724 Downloadable Samples
Illumina human-6 v2.0 expression beadchip, Affymetrix Human Genome U219 Array (hgu219)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Innate immune activity is detected prior to seroconversion in children with HLA-conferred type 1 diabetes susceptibility.
Sample Metadata Fields
Sex, Specimen part
View Samples