Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Gene expression profile of RAW264.7 monocytes treated with or without IL-33

ABSTRACT: Molecular mechanisms underlying the cancer stroma in metastasis is largely unknown. Here we show that cancer-associated fibroblasts (CAFs) produce high levels of IL-33 that acted on tumor-associated macrophages (TAMs) to induce the M1 to M2 transition. Genome profiling of metastasis-related genes in the IL-33-stimulated TAMs showed a > 200-fold increase of metalloproteinase 9 (MMP9). Signaling analysis demonstrated the IL-33-ST2-NFkB-MMP9-laminin pathway that mediates cancer metastasis. In mouse and human fibroblast-rich pancreatic cancers, genetic deletion of IL-33, ST2 and MMP9 markedly blocked metastasis. Pharmacological inhibition of NFkB and MMP9 also blocked cancer metastasis. Deletion of IL-33, ST2 and MMP9 restored laminin, a key basement membrane component associated to tumor microvessels. Together, our data provide novel mechanistic insights on the IL-33-NFkB-MMP9-laminin axis that mediates the CAF-TAM-committed cancer metastasis. Thus, targeting the CAF-TAM-vessel interaction provides an outstanding therapeutic opportunity for cancer treatment.

ORGANISM(S): Mus musculus

PROVIDER: GSE97657 | GEO | 2018/11/30

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

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

Inflammatory cell-derived CXCL3 promotes pancreatic cancer metastasis through a novel myofibroblast-hijacked cancer escape mechanism

Project description:Objective: Pancreatic ductal adenocarcinoma (PDAC) is the most lethal malignancy and lacks effective treatment. We aimed to understand molecular mechanisms of the intertwined interactions between tumor stromal components in metastasis and to provide a new paradigm for PDAC therapy. Design:Two unselected cohorts of 154 and 20 PDAC patients were subjected to correlation between IL-33 and CXCL3 levels and survivals. Unbiased expression profiling, and genetic and pharmacological gain- and loss-of-function approaches were employed to identify molecular signaling in TAMs and myoCAFs. The role of the IL-33-ST2-CXCL3-CXCR2 axis in PDAC metastasis was evaluated in 3 clinically relevant mouse PDAC models and in a zebrafish model. Results: IL-33 was specifically elevated in human PDACs and positively correlated with tumor inflammation in human PDAC patients. CXCL3 was highly upregulated in IL-33-stimulated macrophages that were the primary source of CXCL3. CXCL3 was correlated with poor survival in human PDAC patients. Mechanistically, activation of the IL-33-ST2-Myc pathway attributed to high CXCL3 production. The highest level of CXCL3 was found in PDAC relative to other cancer types and its receptor CXCR2 was almost exclusively expressed in CAFs. Activation of CXCR2 by CXCL3 induced a CAF-to-myoCAF transition and a-SMA was uniquely upregulated by the CXCL3-CXCR2 signaling. Type III collagen was identified as the CXCL3-CXCR2-targeted adhesive molecule responsible for myoCAF-driven PDAC metastasis. Conclusions: Our work provides novel mechanistic insights into understanding PDAC23 metastasis by the TAM-CAF interaction and targeting each of these signaling components would provide an attractive and new paradigm for treating pancreatic cancer.

2021-02-06 | GSE166263 | GEO

Macrophages reprogramming improves immunotherapy of IL-33 in peritoneal metastasis of gastric cancer

Project description:Peritoneal metastasis (PM) has a suppressive tumor immune microenvironment (TIME), which limits the effects of immunotherapy. This study aims to investigate the immunomodulatory effects of intraperitoneal administration of IL-33 on PM-associated TIME. Immunocompetent mice were used to investigate the role of IL-33 in development of abdominal dissemination and host outcome. Murine (m) and human (h) gastric cancer cells were tested for their response to IL-33 by qRT-PCR, flow cytometry, and immunofluorescence. Survival was significantly prolonged in patients with high Il-33 mRNA expression. Intraperitoneal administration of IL-33 could induce the celiac inflammatory environment, activate immunologic effector cells and reverse the immunosuppressive tumor microenvironment, which delayed tumor progression and peritoneal metastasis of gastric cancer. Mechanistically, IL-33 could induce M2 polarization by activating p38-GATA-binding protein 3 (GATA3) signaling pathway. IL-33 combined with anti-CSF1R or p38 inhibitor to regulate tumor-associated macrophages (TAMs) showed synergistic anti-tumor effect. Intraperitoneal administration of IL-33 inducing local inflammatory milieu provided a novel approach for the treatment of metastatic peritoneal malignancies, which combined with TAMs reprogramming to reshape TIME could achieve better treatment efficacy.

2023-06-30 | GSE235526 | GEO

RNA-Sequencing of ST2+ Treg cells in response to IL-33 stimulation

Project description:The effects of IL-33 on ST2+ Treg cells were not studied thouroughly. We FACS-sorted in vitro expanded ST2+ Treg cells from C57BL/6 Foxp3-IRES-mRFP (B6 FIR) mice. We next used RNA-seq techonology to define how recombinant IL-33 (rIL-33) may impact mouse Treg by to assessing the transcriptome of IL-33-stimulated ST2+ Treg cells compared to that of untreated ST2+ Treg cells. Our data revealed that ST2+ Treg stimulated with rIL-33 for 6 hours exhibited increased expression of Il10 and Il13 compared to unstimulated ST2+ Treg cells.

2019-05-17 | GSE123922 | GEO

GDF15 overexpression dreived from tumor-associated macrophages and cancer cells in the microenvironment of human esophageal squamous cell carcinoma promotes tumor growth and poor prognosis

Project description:Tumor-associated macrophages (TAMs) are known to be involved in progression, angiogenesis and motility of various cancers. We have previously reported the association between increased number of infiltrating TAMs with tumor progression and poor prognosis in esophageal squamous cell carcinomas (ESCCs). To study roles of TAMs in ESCC, we first exposed peripheral blood monocytes (PBMo) derived macrophages from healthy volunteers to conditioned media of TE series human ESCC cell line (TECM) and confirmed the induction of expression of M2 macrophage marker, CD204, and protumorigenic factors, interleukin (IL)-10, VEGFA and MMPs. Next, we compared gene expression profile between PBMo-derived macrophages and PBMo-derived macrophages stimulated with TECM by cDNA microarray. Based on the result, we focused on growth differentiation factor 15 (GDF15) among highly expressed genes including IL-6, IL-8 and CXCL1. Immunohistochemical study on 70 cases of surgically resected ESCCs revealed that GDF15 was detected not only in macrophages but also in cancer cells. High expression of GDF15 in ESCCs was significantly correlated with more malignant phenotypes including lymph and blood vessel invasion, lymph node metastasis as well as clinical stages. Patients with high expression of GDF15 showed poor disease-free survival (p = 0.011) and overall survival (p = 0.041). Furthermore, we found that recombinant human GDF15 promote cell proliferation and phosphorylation of both Akt and Erk1/2 in ESCC cell lines in vitro. These results indicate that GDF15 is secreted by both TAMs and cancer cells in tumor microenvironment and is associated with aberrant growth and poor prognosis of human ESCC. We exposed PBMo-derived macrophages from healthy volunteers to TECM and observed their acquisition of TAM-like characters in this study. We further investigated specific cancer-associated gene expression profile in TECM induced TAM-like macrophages by cDNA microarray analysis.

2014-08-01 | E-GEOD-59948 | biostudies-arrayexpress

Expression data of S1M cells sorted high and low after ST2 antibody treatment

Project description:ST2 functions as a receptor for the cytokine IL-33. It has been implicated in carcinogenesis. In this study, we sought to mechanistically determine how ST2 and IL-33 function to support cancer stem cell (CSC) activity and drive gastric cancer (GC) pathogenesis. We used microarrays to detail the global program of gene expression among S1M ST2 high and low cells and to identify distinct classes of genes upregulated in this process.

2023-01-10 | GSE214997 | GEO

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

2015-12-17 | GSE74695 | GEO

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

The alarmin interleukin-33 promotes the expansion and preserves the stemness of Tcf-1+ CD8 T cells in chronic viral infection (RNA-Seq II)

Project description:T-cell factor 1 (Tcf-1) expressing CD8 T cells exhibit stem-like self-renewing capacity rendering them key for immune defense against chronic viral infection and cancer. Yet, the signals that promote the formation and maintenance of these memory-like CD8 T cell (CD8ML) remain poorly defined. Studying CD8 T cell differentiation in mice with chronic viral infection we identify the alarmin interleukin-33 (IL-33) as pivotal for the expansion and stem-like functioning of CD8ML as well as for virus control. IL-33 receptor- (ST2-) deficient CD8 T cells exhibit biased end-differentiation and premature loss of Tcf-1. Intriguingly, ST2-deficient CD8ML responses are restored by blockade of type I interferon signaling, suggesting that opposing IFN-I and IL-33 effects control CD8ML formation in chronic infection. IL-33 signals broadly augment chromatin accessibility in CD8ML and determine these cells’ re-expansion potential. Our study identifies the IL-33 – ST2 axis as an important CD8ML-promoting pathway in the context of chronic viral infection.

2023-04-06 | GSE210538 | GEO

The alarmin interleukin-33 promotes the expansion and preserves the stemness of Tcf-1+ CD8 T cells in chronic viral infection (RNA-Seq I)

2023-04-06 | GSE210537 | 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