Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

RNA-seq analysis of colon tumors collected from St2-/- and WT reciprocal bone marrow chimeric mice treated with azoxymethane.

ABSTRACT: Interleukin 33 (IL33) is an inflammatory cytokine released during necrotic cell death. The epithelium and stroma of the intestine express large amounts of IL33 and its receptor St2. IL33 is therefore continuously released during homeostatic turnover of the intestinal mucosa. Although IL33 can prevent colon cancer associated with inflammatory colitis, the contribution of IL33 signaling to sporadic colon cancer remains unknown. Here, we utilized a mouse model of sporadic colon cancer to investigate the contribution of IL33 signaling to tumorigenesis in the absence of pre-existing inflammation. We demonstrated that genetic ablation of St2 enhanced colon tumor development. In reciprocal bone marrow (BM) chimeras, the concurrent loss of IL33 signaling within radioresistant nonhematopoietic, and the radiosensitive hematopoietic, compartments was associated with increased tumor burden. To elucidate the molecular mechanisms underpinning the tumor-suppressing effect of IL33 signaling in sporadic colon cancer, we performed whole transcriptome analysis of tumors collected from each of the four cohorts of the 6xAOM-treated BM chimeras. We discovered that St2 deficiency within the nonhematopoietic compartment coincided with suppression of an IFN gene expression signature. The decrease of this IFN gene expression signature was associated with more aggressive disease in human colon cancer patients, suggesting that lack of IL33 signaling impaired the generation of a potent IFN-mediated antitumor immune response. Collectively, our data reveal that IL33 functions as a tumor suppressor in sporadic colon cancer.

ORGANISM(S): Mus musculus

PROVIDER: GSE109694 | GEO | 2018/01/27

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Tumor-Infiltrating Regulatory T Cell Accumulation in the Tumor Microenvironment is Mediated by IL33/ST2 Signaling

Project description:Tumor-Infiltrating Regulatory T Cell Accumulation in the Tumor Microenvironment is Mediated by IL33/ST2 Signaling

| PRJNA638113 | ENA

Tumor-Infiltrating Regulatory T Cell Accumulation in the Tumor Microenvironment is Mediated by IL33/ST2 Signaling

Project description:Tumor-Infiltrating Regulatory T Cell Accumulation in the Tumor Microenvironment is Mediated by IL33/ST2 Signaling

| PRJNA492395 | ENA

Spatial profiling of a unique cancer-associated fibroblast population in the tumor microenvironment in sporadic early-onset colon cancer [eocc_pip]

Project description:The incidence of sporadic early-onset colon cancer (EOCC) has increased worldwide. The molecular mechanisms in the tumor and the tumor microenvironment in EOCC are not fully understood. The aim of this study is to unravel unique spatial transcriptomic and proteomic profiles in tumor epithelial cells and cancer-associated fibroblasts (CAFs). Sporadic colon cancer FFPE tissue samples were divided into patients diagnosed with EOCC (<50 yrs) and late-onset colon cancer (LOCC, ≥50 yrs). A total of 13 LOCC and 13 EOCC patients that were analyzed using HTG EdgeSeq Precision Immuno-Oncology Panel. The data generated was combined with in silico analysis and functional assays to characterize FAP(+) CAFs at the EOCC tumor invasive margin.

2023-11-22 | GSE240623 | GEO

Spatial profiling of a unique cancer-associated fibroblast population in the tumor microenvironment in sporadic early-onset colon cancer [eocc]

Project description:The incidence of sporadic early-onset colon cancer (EOCC) has increased worldwide. The molecular mechanisms in the tumor and the tumor microenvironment in EOCC are not fully understood. The aim of this study is to unravel unique spatial transcriptomic and proteomic profiles in tumor epithelial cells and cancer-associated fibroblasts (CAFs). Sporadic colon cancer FFPE tissue samples were divided into patients diagnosed with EOCC (<50 yrs) and late-onset colon cancer (LOCC, ≥50 yrs). Spatial transcriptomic analysis of 112 areas of interest (AOIs) were performed using Nanostring GeoMx digital spatial profiling. The data generated was combined with in silico analysis and functional assays to characterize FAP(+) CAFs at the EOCC tumor invasive margin.

2023-11-22 | GSE240531 | GEO

Pairwise comparison of ST2+ and ST2- FOXP3+ T cells derived from mouse intestinal tumors

Project description:Colorectal cancer (CRC) was induced in Foxp3/eGFP reporter mice by the azoxymethane/dextran sulphate sodium salt (AOM/DSS) protocol. Mice were injected i.p. with the procarcinogen AOM (12.5 mg/kg of body weight). After 1 week, mice received drinking water supplemented with 2.5% DSS for 5 to 7 days, followed by 2 weeks of regular water. The DSS administration was repeated twice with 2% DSS. Mice were sacrificed at week 11 and lamina propia lymphocytes (LPLs) from the colon were isolated. CD4+FOXP3+ (eGFP+) ST2+ or ST2- Tregs were separated from colonic LPLs of CRC induced mice using a FACSAria II cell sorter. Microarray analysis was performed to analyze if ST2+ FOXP3+ Tregs from the colon of CRC mice present a distinct transcription pattern compared to ST2- FOXP3+ Tregs. By this, the role of ST2 for Treg function during intestinal tumorigenesis should be characterized.

2019-05-31 | E-MTAB-6842 | biostudies-arrayexpress

The alarmin IL-33 amplifies an immune response in the degenerating retina

Project description:ST2 heterodimerizes with IL-1RAcp to form the receptor for IL-33, which is primarily associated with allergic inflammation by inducing Th2 responses. Recently, however, IL-33 was found to be expressed in the central nervous system and in retinal Muller cells which imply functions, as yet undescribed, beyond Th2 mediated inflammation. Muller cells support the health of the retina and photoreceptors and are also involved in inflammation in retinal degeneration. It is not known how IL-33/ST2 functions in this capacity. We recently found that ST2 ko mice are protected from CLE-induced photoreceptor loss, implying a detrimental effect of IL33/ST2 in CLE. We wish to perform microarray analysis using WT and ST2 KO mice in CLE model to better understand the mechanism by which IL-33/ST2 regulates retinal degeneration. CLE (Constant Light Exposure) is a model of retinal damage/degeneration in mice. Mice are exposed to bright light 24 hours a day for a period of time which damages retina photoreceptors. This damage is assessed by histology, optical coherence tomography (OCT), which measures retina thickness in vivo. In this experiment, the WT and ST2 KO mice (5 mice per genotype per time point) will be exposed to 1200-lux constant light for 0, 3, 10 days. The retinal RNA will be isolated and analyzed for differential gene expression by microarray.

2015-12-17 | E-GEOD-74695 | biostudies-arrayexpress

Interleukin-23 receptor signaling in regulatory T cells in a mouse model of inflammation-associated cancer.

Project description:The pro-inflammatory cytokine interleukin-23 (IL-23) has been implicated in colorectal carcinogenesis (CRC). Yet, the cell-specific contributions of IL-23 receptor (IL-23R) signaling in CRC remain unknown. One of the cell types that highly expresses IL-23R are colonic regulatory T cells (Treg cells). The aim of this study was to define the contribution of Treg cell-specific IL-23R signaling in sporadic and inflammation-associated CRC. In mice, the role of IL-23R in Treg cells in colitis-associated cancer (CAC) was investigated using azoxymethane/dextran sodium sulphate in wild-type Treg cell reporter mice (WT, Foxp3YFP-Cre), and mice harboring a Treg cell-specific deletion of IL-23 (Il23rΔTreg). Il23rΔTreg mice had increased dysplasia compared to WT mice associated with decreased tumor-infiltrating macrophages. The role of Treg cell IL-23R in sporadic CRC was examined via orthotopic injection of the syngeneic colon cancer cell line MC-38 submucosally into the colon/rectum of mice. In the sporadic cancer model, Il23rΔTreg mice had increased survival and decreased tumor size compared to WT mice. Additionally, MC-38 tumors of Il23rΔTreg mice had a higher frequency of pro-inflammatory macrophages and IL-17 producing CD4+ T cells. This data suggests that loss of IL-23R signaling in Treg cells permits IL-17 production by CD4+ T cells that in turn promotes pro-inflammatory macrophages to clear tumors. These findings further support and highlight the importance of selecting a physiologically relevant model based on the type of cancer in which to evaluate the role of specific genes in late tumorigenesis. Finally, single-cell RNA-seq analysis of a previously published dataset in human sporadic cancer, revealed that IL23R was highly expressed in CRC compared to other cancers and specifically in tumor-associated Treg cells.

2024-02-28 | GSE240707 | GEO

The alarmin IL-33 amplifies an immune response in the degenerating retina

2015-12-17 | GSE74695 | GEO

Gene expression profile of F4/80+ cells isolated from tumors implanted in wild type and St2-/- mouse

Project description:We report a novel mechanism of the interaction between perivascular cell and TAMs in promoting metastasis through the IL-33-ST2-dependent pathway. IL-33 was the highest up-regulated gene through activation of SOX7 transcription factor in PDGF-BB-stimulated pericytes. Gain- and loss-of-function experiments validate that IL-33 promotes metastasis through recruitment of TAMs. Il33-/- deficient mice showed impaired TAM recruitment and metastasis. Pharmacological inhibition of the IL-33-ST2 signalling by a soluble ST2 significantly inhibited TAMs and metastasis. Genetic deletion of host IL-33 in mice also blocked PDGF-BB-induced TAM recruitment and metastasis. High IL-33 in human cancers correlated with poor survival prognosis. These findings shed novel mechanisms of tumour stroma in promoting metastasis and have therapeutic implications for cancer therapy.

2016-05-03 | GSE69402 | GEO

Gene expression profiling of colitis-associated and sporadic colorectal tumors in mice

Project description:To uncover molecular mechanisms specifically involved in the pathogenesis of colitis-associated colon cancer (CAC), we studied tumorigenesis in experimental models of CAC and sporadic CRC that mimic characteristics of human CRC. Using comparative whole genome expression profiling, we observed differential expression of epiregulin (Ereg) in mouse models of colitis-associated, but not sporadic colorectal cancer. Similarly, highly significant upregulation of Ereg expression was found in cohorts of patients with colitis-associated cancer in inflammatory bowel disease but not in sporadic colorectal cancer. Furthermore, tumor-associated fibroblasts were identified as major source of Ereg in colitis-associated neoplasias. Functional studies showed that Ereg-deficient mice, although more prone to colitis, are strongly protected from colitis-associated tumors, and data from serial endoscopic studies revealed that Ereg promotes growth rather than initiation of tumors. 4 samples of individual distal colitis-associated tumors (CAC) from 4 mice, 2 samples of tumor-free distal colon epithelium with a pool of 5 mice per sample (CAC contr), 5 samples of individual Apcmin/+ tumors from the distal colorectum of 5 mice (sporCRC) and 3 samples of tumor-free distal colon epithelium (pool of 4 mice per sample) (sporCRC contr). Colitis-associated tumorigenesis was performed by intraperitoneal injection of Azoxymethane (10mg/kg) (Sigma) into C57BL/6J wildtype mice followed by 3 cycles of Dextran Sodium Sulfate (DSS) in drinking water. Each DSS-cycle was composed of DSS (2.5% (w/v) (MP Biomedicals) in drinking water for 7 days, followed by a recovery phase with regular drinking water for 14 days. Sporadic tumors were from C57BL/6J-ApcMin/+/J mice. All tumors were obtained from the from the lower 6th of the large intestine and they had the same size covering between Â¼ and up to Â½ of the colonic circumferenc as evaluated by mini-endoscopy.

2013-04-01 | E-GEOD-43338 | biostudies-arrayexpress

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