Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Expression analysis of tumor microenvironment in triple-negative breast carcinoma in xenograft model

ABSTRACT: Decorin, a member of the small leucine-rich proteoglycan gene family, exists and functions wholly within the tumor microenvironment to suppress tumorigenesis by directly targeting and antagonizing multiple receptor tyrosine kinases, such as the EGFR and Met. This leads to potent and sustained signal attenuation, growth arrest, and angiostasis. We thus sought to evaluate the tumoricidal benefits of systemic decorin on a triple-negative orthotopic breast carcinoma xenograft model. To this end, we employed a novel high-density mixed expression array capable of differentiating and simultaneously measuring gene signatures of both Mus musculus (stromal) and Homo sapiens (epithelial) tissue origins. We found decorin modulated the differential expression of 374 genes within the stromal compartment of the tumor xenograft. Further, our top gene ontology classes strongly suggests an unexpected and preferential role for decorin to inhibit genes necessary for immunomodulatory responses, while simultaneously inducing expression of those possessing cellular adhesion and tumor suppressive gene properties. Rigorous verification of the top scoring candidates led to the discovery of three genes heretofore unlinked to malignant breast cancer that were reproducibly found to be induced in several models of tumor stroma. Collectively, our data provide highly novel and unexpected stromal gene signatures as a direct function of systemic decorin administration and reveals a fundamental basis of action for decorin to modulate the tumor stroma as a biological mechanism for the ascribed anti-tumorigenic properties.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE37937 | GEO | 2012/05/12

SECONDARY ACCESSION(S): PRJNA165707

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Expression analysis of tumor microenvironment in triple-negative breast carcinoma in xenograft model

Project description:Decorin, a member of the small leucine-rich proteoglycan gene family, exists and functions wholly within the tumor microenvironment to suppress tumorigenesis by directly targeting and antagonizing multiple receptor tyrosine kinases, such as the EGFR and Met. This leads to potent and sustained signal attenuation, growth arrest, and angiostasis. We thus sought to evaluate the tumoricidal benefits of systemic decorin on a triple-negative orthotopic breast carcinoma xenograft model. To this end, we employed a novel high-density mixed expression array capable of differentiating and simultaneously measuring gene signatures of both Mus musculus (stromal) and Homo sapiens (epithelial) tissue origins. We found decorin modulated the differential expression of 374 genes within the stromal compartment of the tumor xenograft. Further, our top gene ontology classes strongly suggests an unexpected and preferential role for decorin to inhibit genes necessary for immunomodulatory responses, while simultaneously inducing expression of those possessing cellular adhesion and tumor suppressive gene properties. Rigorous verification of the top scoring candidates led to the discovery of three genes heretofore unlinked to malignant breast cancer that were reproducibly found to be induced in several models of tumor stroma. Collectively, our data provide highly novel and unexpected stromal gene signatures as a direct function of systemic decorin administration and reveals a fundamental basis of action for decorin to modulate the tumor stroma as a biological mechanism for the ascribed anti-tumorigenic properties. A twelve-array (three arrays per slide) study using total RNA extracted from twelve individual SCID mice with established MDA-MB-231 orthotopic tumor xenografts (n=6 per cohort) treated systemically with decorin for 23 days at 10mg/kg via intraperitneal injections.

2012-05-11 | E-GEOD-37937 | biostudies-arrayexpress

Multi-omics profiling of non-small cell lung cancer patient-derived xenografts reveals proteome and phosphoproteome remodeling associated with patient outcome

Project description:131 patient-derived xenograft models were generated for non-small cell lung carcinoma and were profiled by analysis of gene copy number variation, whole exome sequence, methylome, transcriptome, proteome, and phospho(Tyr)-proteome. Proteome profiling resolved the known major histology subtypes and revealed 3 proteome subtypes (proteotypes) among adenocarcinoma and 2 in squamous cell carcinoma that were associated with distinct protein-phosphotyrosine signatures and patient survival. Proteomes of human tumor were discernible from murine stroma. Stromal proteomes were similar between histological subtypes, but two adenocarcinoma proteotypes had distinct stromal proteomes. Tumor and stromal proteotypes comprise signatures of targetable biological pathways suggesting that patient stratification by proteome profiling may be an actionable approach to precisely diagnose and treat cancer.

2021-11-24 | PXD016579 | Pride

Label-free proteomics quantification of pancreatic ductal adenocarcinoma patient-derived xenografts with treatment combining Gemcitabine and nab-Paclitaxel

Project description:Tumor-stroma interactions are critical in pancreatic ductal adenocarcinoma (PDAC) progression and therapeutics. Patient-derived xenograft (PDX) models faithfully recapitulate tumor-stroma interactions in PDAC, but conventional antibody-based immunoassay is largely inadequate to resolve or quantify tumor and stromal proteins. A species-deconvolved proteomics approach embedded in the ultra-high-resolution (UHR)-IonStar workflow can unambiguously quantify the proteins from tumor (human-derived) and stroma (mouse-derived) in PDX samples, enabling unbiased investigation of their proteomes with excellent quantitative reproducibility. With this strategy, 3 PDAC PDXs were analyzed. They were showed differential responses to treatment with Gemcitabine combined with nab-Paclitaxel (GEM+PTX), which is a first-line treatment regimen for PDAC. For each PDAC PDX, samples were collected after 24 hour and 192 hour with/without treatment, and each condition contained four biological replicates.

2023-07-05 | PXD042267 | Pride

Multi-omics profiling of non-small cell lung cancer patient-derived xenografts reveals proteome and phosphoproteome remodeling associated with patient outcome

Project description:131 patient-derived xenograft models were generated for non-small cell lung carcinoma and were profiled at the genome, transcriptome and proteome level by analysis of gene copy number variation, whole exome sequencing, DNA methylation, transcriptome, proteome and phospho(Tyr)-proteome. At the proteome level, the human tumor and murine stroma were discernible. Tumor proteome profiling resolved the known major histological subtypes and revealed 3 proteome subtypes (proteotypes) among adenocarcinoma and 2 in squamous cell carcinoma that were associated with distinct protein-phosphotyrosine signatures and patient survival. Stromal proteomes were similar between histological subtypes, but two adenocarcinoma proteotypes had distinct stromal proteomes. Proteotypes comprise tumor and stromal signatures of targetable biological pathways suggesting that patient stratification by proteome profiling may be an actionable approach to precisely diagnose and treat cancer.

2021-11-24 | PXD016674 | Pride

Simultaneous analysis of tumor and stromal gene expression profiles from xenograft models

Project description:Identifying the gene expression alterations that occur in both the tumor and stroma is essential to understanding tumor biology. We have developed a dual-species microarray analysis method that allows the dissection of both tumor and stromal gene expression profiles from xenograft models, based on limited interspecies cross-hybridization on Illumina gene expression beadchips. This methodology allows for simultaneous genome-wide analysis of gene expression profiles of both tumor cells and the associated stromal tissue. Data is provided regarding the crosshybridization of mouse liver RNA on human microarray, and MDA-MB-231 breast cancer cell line RNA on mouse microarray. Data is also provided for comparisons of MDA-MB-231 gene expression in vitro vs. in vivo, and mouse liver gene expression in control mice vs. stroma from MDA-MB-231 xenograft liver metastasis in tumor bearing mice A total of 18 samples were analyzed. Samples consist of 6 different types with each type in triplicate. Types are (1) MDA-MB-231 cell line grown in vitro and arrayed on mouse chips, (2) mouse liver from NOD/SCID mice arrayed on human chips, (3) MDA-MB-231 cell line grown in vitro arrayed on human chips, (4) MDA-MB-231 xenograft liver metastasis arrayed on human chips, (5) mouse liver from NOD/SCID mice arrayed on mouse chips, and (6) MDA-MB-231 xenograft liver metastasis arrayed on mouse chips. The overall design had three objectives: (1) to determine crosshybridizing probes based on sample types 1, 2, 3, and 5, (2) detect stromal and tumor expression using sample types 4 and 6, and (3) determine genes differentially expressed in tumor or metastasis compared to normal by comparing sample types 3 and 4 and comparing sample types 1 and 5.

2011-11-22 | E-GEOD-30993 | biostudies-arrayexpress

Simultaneous analysis of tumor and stromal gene expression profiles from xenograft models

2011-11-22 | GSE30993 | GEO

ECM deposition is driven by caveolin1-dependent regulation of exosomal biogenesis and cargo sorting

Project description:The composition and physical properties of the extracellular matrix (ECM) critically influence tumor progression, but the molecular mechanisms underlying ECM layering are poorly understood. Tumor-stroma interaction is critically dependent on cell-cell communication mediated by exosomes, small vesicles generated within multivesicular bodies (MVBs). Here, we show that caveolin-1 (Cav1) is a central modulator of both exosome biogenesis and exosomal protein cargo sorting through the regulation of cholesterol content at the endosomal compartment/MVBs. Quantitative proteomics profiling revealed that Cav1 is required for exosomal sorting of ECM protein cargo subsets including tenascin-C (TnC), and for fibroblast-derived exosomes to efficiently depose ECM and promote tumor cell invasiveness. Cav1-driven exosomal ECM deposition not only promotes local stromal remodeling, but also the generation of distant ECM-enriched stromal niches. These results support a model by which Cav1 is a central regulatory hub for tumor-stroma interactions through a novel exosome-dependent ECM deposition mechanism. Linked studies: <a href='https://www.ebi.ac.uk/metabolights/MTBLS1969' rel='noopener noreferrer' target='_blank'>MTBLS1969</a>

2020-10-07 | MTBLS1977 | MetaboLights

ECM deposition is driven by caveolin1-dependent regulation of exosomal biogenesis and cargo sorting

Project description:The composition and physical properties of the extracellular matrix (ECM) critically influence tumor progression, but the molecular mechanisms underlying ECM layering are poorly understood. Tumor-stroma interaction is critically dependent on cell-cell communication mediated by exosomes, small vesicles generated within multivesicular bodies (MVBs). Here, we show that caveolin-1 (Cav1) is a central modulator of both exosome biogenesis and exosomal protein cargo sorting through the regulation of cholesterol content at the endosomal compartment/MVBs. Quantitative proteomics profiling revealed that Cav1 is required for exosomal sorting of ECM protein cargo subsets including tenascin-C (TnC), and for fibroblast-derived exosomes to efficiently depose ECM and promote tumor cell invasiveness. Cav1-driven exosomal ECM deposition not only promotes local stromal remodeling, but also the generation of distant ECM-enriched stromal niches. These results support a model by which Cav1 is a central regulatory hub for tumor-stroma interactions through a novel exosome-dependent ECM deposition mechanism. Linked studies: <a href='https://www.ebi.ac.uk/metabolights/MTBLS1977' rel='noopener noreferrer' target='_blank'>MTBLS1977</a>

2020-10-07 | MTBLS1969 | MetaboLights

Characteristics of Cross-Hybridization and Cross-Alignment in Pseudo-Xenograft samples by RNA-Seq and Microarrays [RNA-Seq]

Project description:In order to study molecular changes in the stroma from tissue samples it is recommended to separate tumor tissue from stromal tissue. This is particularly relevant to mouse tumor xenograft models where tumor, particularly metastatic tumors, can be small and difficult to separate from the host tissue. In our research we compared qualitatively the ability of high-throughput mRNA sequencing, RNA-Seq, and microarrays to detect tumor (human) and stromal (mouse) expression from mixed tumor-stromal samples in terms of the genes and pathways that are involved in cross-alignment (RNA-Seq) and cross-hybridization (microarrays).

2012-12-14 | GSE40890 | GEO

Characteristics of Cross-Hybridization and Cross-Alignment in Pseudo-Xenograft samples by RNA-Seq and Microarrays [Illumina MouseWG-6 v2.0]

2012-12-14 | GSE40868 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data