Browse
Submit Data
Databases
API
Help

Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

16 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Effect of enforced BMP4 expression on gene expression profile of 4T1.2 whole primary murine mammary tumours

ABSTRACT: BMP4 is down-regulated in metastatic human and murine mammary tumours. Here we determined the effect of ectopic mouse Bmp4 re-expression on global gene expression patterns in orthotopic primary mammary tumours in syngeneic Balb/c mice. Breast cancer is a major cause of cancer related death in women, due to the development of metastatic disease in vital organs. Metastasis can be facilitated by tumor induced MDSC, which requires understanding. We have confirmed that BMP4 is a potent suppressor of breast cancer metastasis, but for potential clinical application, it is important to understand how BMP4 acts to suppress metastasis. Here, we report one mechanism by which BMP4 can inhibit metastasis. Mice bearing highly metastatic mammary tumors present with elevated numbers of myeloid derived suppressor cells (MDSC), the extent of which is markedly reduced upon exogenous BMP4 expression. Increased numbers of MDSC can also be induced directly by treatment with granulocyte-colony stimulating factor (G-CSF), leading to enhancement of metastasis. Both tumor-induced and G-CSF-induced MDSC can effectively suppress T cell activation and proliferation. BMP4 acts to reduce the expression and secretion of G-CSF through inhibition of NFkB activity in several human and mouse tumor lines. Since MDSC in breast cancer patients are correlated with poor prognosis, BMP4 treatment offers a potential new therapeutic strategy for progressive breast disease. Three 4T1.2 primary mammary tumours and three 4T1.2-Bmp4 primary mammary tumours were analyzed.

ORGANISM(S): Mus musculus

SUBMITTER: Cameron Johnstone

PROVIDER: E-GEOD-51632 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Json Xml

Similar Datasets

Effect of enforced BMP4 expression on gene expression profile of 4T1.2 whole primary murine mammary tumours

Project description:BMP4 is down-regulated in metastatic human and murine mammary tumours. Here we determined the effect of ectopic mouse Bmp4 re-expression on global gene expression patterns in orthotopic primary mammary tumours in syngeneic Balb/c mice. Breast cancer is a major cause of cancer related death in women, due to the development of metastatic disease in vital organs. Metastasis can be facilitated by tumor induced MDSC, which requires understanding. We have confirmed that BMP4 is a potent suppressor of breast cancer metastasis, but for potential clinical application, it is important to understand how BMP4 acts to suppress metastasis. Here, we report one mechanism by which BMP4 can inhibit metastasis. Mice bearing highly metastatic mammary tumors present with elevated numbers of myeloid derived suppressor cells (MDSC), the extent of which is markedly reduced upon exogenous BMP4 expression. Increased numbers of MDSC can also be induced directly by treatment with granulocyte-colony stimulating factor (G-CSF), leading to enhancement of metastasis. Both tumor-induced and G-CSF-induced MDSC can effectively suppress T cell activation and proliferation. BMP4 acts to reduce the expression and secretion of G-CSF through inhibition of NFkB activity in several human and mouse tumor lines. Since MDSC in breast cancer patients are correlated with poor prognosis, BMP4 treatment offers a potential new therapeutic strategy for progressive breast disease.

2014-06-01 | GSE51632 | GEO

Breast Cancer Non-Glyco

Project description:Breast cancer is a very common disease in women and its treatment is complicated due to its very heterogeneous nature. The outcome of treatment is consequently highly variable, some patients respond completely to surgical removal of the primary tumour whilst others suffer progression and metastasis regardless of (neo-) adjuvant therapy. Here we present an analysis of a second overlapping set of paired tumours, both synchronous local and asynchronous distant metastases. We show the most significant changes in intracellular protein expression occur in the enzymes involved in pathways of glycoprotein synthesis and decoration during progression, in remodelling of the extra-cellular matrix and in changes in protein translation initiation.

2022-03-01 | PXD006719 | Pride

Mus musculus

Project description:Effect of enforced BMP4 expression on gene expression profile of 4T1.2 whole primary murine mammary tumours

| PRJNA224138 | ENA

RNA-seq expression profiling of murine breast tumor cell lines

Project description:Breast tumour cells were found to remodel the bone marrow vascular microenviornment to support metastatic expansion. To identify tumour-derived factors that stimulate marrow endothelium, we studied the transcriptomes of four isogenic murine mammary tumour cell lines, 4T1.2, 4T1, 66cl4 and 67NR.

2021-09-16 | GSE160101 | GEO

Interferon Regulatory Factor-8, an Integral Determinant of Myeloid-Derived Suppressor Cell Subset Development

Project description:Myeloid-derived suppressor cells (MDSC) are a major barrier to anticancer responses. Although much is known about how MDSC promote tumor progression, little is known about how they develop. We hypothesized that MDSC develop as a consequence of tumor-induced downregulation of interferon regulatory factor-8 (IRF-8), a key myeloid developmental transcription factor. We showed that: 1) IRF8-deficiency in mice generated myeloid populations highly homologous to tumor-induced MDSC; 2) IRF-8 overexpression in mice reduced MDSC accumulation and retarded tumor growth; 3) MDSC-inducing factors, G-CSF or GM-CSF, facilitated IRF-8 downregulation via STAT3- or STAT5-dependent pathways, respectively; and 4) IRF-8 levels in MDSC-like subsets of breast cancer patients were depressed compared to healthy donors. Altogether, our data implicate IRF-8 as a novel MDSC-dependent transcription factor. Splenic CD11b+Gr-1high cell populations from tumor-bearing mice, IRF8 knockout mice or non-tumor-bearing control mice were purified in two independent experiments by flow cytometry (> 97% purity) and subjected to whole genome expression profiling using Illumina microarrays.

2013-07-05 | E-GEOD-39228 | biostudies-arrayexpress

Loss of tumor-derived SMAD4 enhances primary tumor growth but not metastasis following BMP4 signalling

Project description:We have reported previously that in preclinical models, BMP4 is a potent inhibitor of breast cancer metastasis and that high BMP4 protein levels predict favourable patient outcome. Here, we investigated the requirement for functional SMAD4 in mediating the anti-metastatic response of BMP4, given reports of promotion of metastasis by BMP4 in cancers where SMAD4 is frequently deleted. BMP4-induced inhibition of metastasis does not require functional SMAD4 in tumor cells. However, tumor cell intrinsic signalling using a constitutively active BMP receptor does require functional SMAD4 to suppress metastasis, thus implicating BMP4 mediated paracrine signalling as a contributor to the inhibition of metastasis.

2024-04-30 | GSE199628 | GEO

Myeloid-derived suppressor cell development is regulated by a STAT/IRF-8 axis

Project description:Interferon Regulatory Factor-8, an Integral Determinant of Myeloid-Derived Suppressor Cell Subset Development. Myeloid-derived suppressor cells (MDSC) are a major barrier to anticancer responses. Although much is known about how MDSC promote tumor progression, little is known about how they develop. We hypothesized that MDSC develop as a consequence of tumor-induced downregulation of interferon regulatory factor-8 (IRF-8), a key myeloid developmental transcription factor. We showed that: 1) IRF8-deficiency in mice generated myeloid populations highly homologous to tumor-induced MDSC; 2) IRF-8 overexpression in mice reduced MDSC accumulation and retarded tumor growth; 3) MDSC-inducing factors, G-CSF or GM-CSF, facilitated IRF-8 downregulation via STAT3- or STAT5-dependent pathways, respectively; and 4) IRF-8 levels in MDSC-like subsets of breast cancer patients were depressed compared to healthy donors. Altogether, our data implicate IRF-8 as a novel MDSC-dependent transcription factor.

2013-07-05 | GSE39228 | GEO

p140Cap overexpression in Balb-neuT HER2 breast cancer transgenic mice

Project description:In HER2-positive breast cancer patients the adaptor protein p140Cap correlates with increased patient survival and decreased probability to develop metastasis. Causally, p140Cap negatively regulates in vitro and in vivo breast tumor properties. Here we show that p140Cap status correlates with a rewiring of the tumor immune microenvironment, with an increased presence of tumor-infiltrating lymphocytes (TILs) in human breast cancers and an inverse correlation with inflammatory hallmarks. Preclinical syngeneic p140Cap models show a significant increase of CD8+ T-Lymphocytes, NK cells and M1-macrophages in p140Cap tumors, a reduced mobilization and a decreased recruitment of G-CSF-dependent Myeloid-Derived Suppressor Cells (MDSC), with a specific reduction in G-CSF mRNA and protein levels. Indeed, p140Cap impacts on the G-CSF axis by reducing the fraction of Tumour-Initiating Cells (TICs) that exhibit an enhanced G-CSF production. Interestingly, p140Cap affects the TIC compartment by limiting the active β-Catenin intracellular pool, stabilizing the destruction complex. These findings identify a novel role of p140Cap in preventing the development of an immunosuppressive tumor promoting microenvironment in Breast Cancer.

2022-12-19 | GSE176229 | GEO

Mus musculus

Project description:Comparison of matched primary and metastasis 4T1.2 syngeneic mammary tumor model of spontaneous bone metastasis

| PRJNA165849 | ENA

Expression data from in vitro differentiated MDSC

Project description:MDSC (myeloid-derived suppressor cells) can be differentiated in vitro using IL-6 and GM-CSF. To identify the specific role of IL-6 in this process, we used microarray to compare MDSC differentiated with IL-6 and GM-CSF to MDSC differentiated with GM-CSF alone. We have found genes and pathways that are up- or downregulated when IL-6 is present.

2020-08-19 | GSE148293 | 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