Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

DNA methylation signature defines genes modulated by stromal cell contents of human breast tumors [MethylationEPIC]

ABSTRACT: Using genome-wide approaches we have identified groups of genes modulated by CAF-secreted factors from human breast cancer cell lines grown in different CAF-conditioned medium. The genes modulated by CAF secreted factors were characterized by a specific DNA methylation pattern: hypermethylation at transcription start site (TSS) and shore regions. Approximately 60% of them exhibited a methylation-dependent expression level and 20% of them were also dependent on the methyl-CpG-binding protein domain 2. Thus, these specific DNA methylation patterns were linked to an epigenetic control of their expression, upon CAF-secreted factors. We have therefore identified some molecular events defining the responsiveness of groups of genes to stromal cell contents in human breast tumors.

ORGANISM(S): Homo sapiens

PROVIDER: GSE95460 | GEO | 2018/02/22

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

DNA methylation signature defines genes modulated by stromal cell contents of human breast tumors [RNA-seq]

Project description:Using genome-wide approaches, we have identified groups of genes modulated by CAF-secreted factors from human breast cancer cell lines grown in different CAF-conditioned medium. The genes modulated by CAF secreted factors were characterized by a specific DNA methylation pattern: hypermethylation at transcription start site (TSS) and shore regions. Approximately 60% of them exhibited a methylation-dependent expression level and 20% of them were also dependent on the methyl-CpG-binding protein domain 2. Thus, these specific DNA methylation patterns were linked to an epigenetic control of their expression, upon CAF-secreted factors. We have therefore identified some molecular events defining the responsiveness of groups of genes to stromal cell contents in human breast tumors.

2018-02-22 | GSE95461 | GEO

Illumina Infinium MethylationEPIC BeadChip (850k) data of primary cancer-associated fibroblasts (CAF) isolated from fresh ex vivo germ cell tumor (GCT) patient tissue

Project description:Illumina Infinium MethylationEPIC BeadChip (850k) array analysis of DNA methylation of primary CAF isolated from fresh ex vivo GCT patient tissue. Purity of CAF populations were verified by qPCR analysis of common CAF, GCT, endothelial and epithelial markers. 14 different CAF cultures from distinct GCT subtypes (seminoma(SE), non-seminoma(NS)) and 5 non-malignant fibroblast cultures were analyzed.

2024-06-21 | GSE228405 | GEO

DNA methylation signature defines genes modulated by stromal cell contents of human breast tumors

Project description:DNA methylation signature defines genes modulated by stromal cell contents of human breast tumors

| PRJNA377159 | ENA

STAT3 induces breast cancer growth and progression via IL-6, STC1 and MMP13 secretion by Cancer Associated Fibroblasts

Project description:In the tumor microenvironment, Cancer Associated Fibroblasts (CAFs) become activated by cancer cells and increase their secretory activity to produce soluble factors that contribute to tumor cells proliferation, invasion and dissemination to distant organs. The pro-tumorigenic transcription factor STAT3 and its canonical inducer, the pro-inflammatory cytokine IL-6 act conjunctly in a positive feedback loop that maintains high levels of IL-6 secretion and STAT3 activation in both tumor and stromal cells. Here, we demonstrate that STAT3 is essential for the pro-tumorigenic functions of murine breast cancer CAFs both in vitro and in vivo, and identify a STAT3 signature significantly enriched for genes encoding for secreted proteins. Among those, IL-6, ANGPTL4, STC-1 and MMP13 were validated as STAT3-dependent mediators of CAF pro-tumorigenic functions by different approaches. CAFs activities were moreover impaired by IL-6 Receptor blocking antibodies and by MMP13 inhibition, supporting the feasibility of a therapeutic approach based on inhibiting STAT3-induced CAF-secreted proteins. The usefulness of such an approach is supported by the observation that an equivalent CAF-STAT3 signature in humans is expressed at high levels in breast cancer stromal cells and characterizes patients with a shorter disease specific survival, including those with basal-like disease.

2021-12-31 | GSE178081 | GEO

Sequencing Facilitates Quantitative Analysis of gene expression among 3 stromal cell populations: NAF, CAF, CAF_HiP

Project description:Purpose : Primary cultured fibroblast cultures can be classified based on their tumor promoting ability. Normal associated fibroblasts (NAF) cannot transform benign epithelia. Cancer associated fibroblasts (CAF) can transform benign epithelia into cancer. As described in Kato and Placencio et al., High passage CAF (CAF_HiP) cells have lost the ability to potentiate tumor growth. This study sought to identify the differences among three groups of fibroblasts: NAF, CAF, and CAF_HiP Methods :Human male prostatectomy tissues were cultured to generate primary cultured fibroblast cultures. Results and Conclusions : Differential gene expression among the top 200 genes analzed as described in Kato and Placencio et al. revealed 33 secreted proteins. SFRP1 was confirmed to be highly expressed in CAF and was shown to play a role in prostate cancer tumor progression and neuroendocrine differentiation.

2019-06-01 | GSE99744 | GEO

Chemotherapy-induced complement signaling modulates immunosuppression and metastatic relapse in breast cancer [RNA-seq]

Project description:Mortality from breast cancer is almost exclusively a result of tumor metastasis and resistance to therapy and therefore understanding the underlying mechanisms is an urgent challenge. Chemotherapy, routinely used to treat breast cancer, induces extensive tissue damage, eliciting an inflammatory response that may hinder efficacy and promote metastatic relapse. Here we show that systemic treatment with chemotherapy following resection of a triple-negative breast tumor induced the expression of complement factors in lung fibroblasts and modulated an immunosuppressive metastatic niche that supported lung metastasis. CAF-derived complement signaling mediated the recruitment of myeloid-derived suppressor cells (MDSCs) to the metastatic niche, thus promoting T cell dysfunction. Functionally, we show that pharmacological targeting of complement signaling in combination with chemotherapy alleviated immune dysregulation and attenuated lung metastasis. Our findings suggest that combining cytotoxic treatment with blockade of complement signaling in triple-negative breast cancer patients may attenuate the adverse effects of chemotherapy, thus offering a promising approach for clinical use.

2022-09-01 | GSE208289 | GEO

Chemotherapy-induced complement signaling modulates immunosuppression and metastatic relapse in breast cancer

Project description:Mortality from breast cancer is almost exclusively a result of tumor metastasis and resistance to therapy and therefore understanding the underlying mechanisms is an urgent challenge. Chemotherapy, routinely used to treat breast cancer, induces extensive tissue damage, eliciting an inflammatory response that may hinder efficacy and promote metastatic relapse. Here we show that systemic treatment with doxorubicin, but not cisplatin, following resection of a triple-negative breast tumor induced the expression of complement factors in lung fibroblasts and modulated an immunosuppressive metastatic niche that supported lung metastasis. CAF-derived complement signaling mediated the recruitment of myeloid-derived suppressor cells (MDSCs) to the metastatic niche, thus promoting T cell dysfunction. Pharmacological targeting of complement signaling in combination with chemotherapy alleviated immune dysregulation and attenuated lung metastasis. Our findings suggest that combining cytotoxic treatment with blockade of complement signaling in triple-negative breast cancer patients may attenuate the adverse effects of chemotherapy, thus offering a promising approach for clinical use.

2022-09-12 | GSE207990 | GEO

Cancer-associated Fibroblast Spatial Heterogeneity and EMILIN1 Expression in Cancer Stroma Modulate TGF-b Activity and CD8+ T-Cell Infiltration in Breast Cancer

Project description:The tumor microenvironment (TME) and its multifaceted interactions with cancer cells are major targets for cancer treatment. Single-cell technologies have brought major insights into the TME, but the resulting complexity frequently precludes conclusions on function. Therefore, we combined single-cell RNA sequencing and spatial transcriptomic data to explore the relationship between different cancer-associated fibroblast (CAF) populations and immune cell exclusion in breast tumors. Our data show for the first time the degree of spatial organization of different CAF populations in breast cancer. We found that IL-iCAFs, Detox-iCAFs, and IFNγ-iCAFs tended to cluster together, while Wound-myCAFs, TGFb-myCAFs, and ECM-myCAFs formed another group that overlapped with elevated TGF-b signaling. Differential gene expression analysis of areas with CD8+ T-cell infiltration/exclusion within the TGF-b signaling-rich zones identified elastin microfibrillar interface protein 1 (EMILIN1) as a top modulated gene. EMILIN1, a TGF-b inhibitor, was upregulated in IFNγ-iCAFs directly modulating TGFb immunosuppressive function. Histological analysis of 74 breast cancer samples confirmed that high EMILIN-1 expression in the tumor margins was related to high CD8+ T-cell infiltration, consistent with our spatial gene expression analysis. High EMILIN-1 expression was also associated with better prognosis of patients with breast cancer, underscoring its functional significance for the recruitment of cytotoxic T cells into the tumor area. In conclusion, our data show that correlating TGF-b signaling to a CAF subpopulation is not enough because proteins with TGF-b-modulating activity originating from other CAF subpopulations can alter its activity. Therefore, therapeutic targeting should remain focused on biological processes rather than on specific CAF subtypes.

2024-04-16 | GSE243022 | GEO

Notch1 - WISP1 Axis Determines Tumor-Regulating Role of Melanoma Stromal Fibroblasts

Project description:Cancer-associated fibroblasts (CAF) are crucial in regulating cancer progression, yet the molecular mechanisms that determine the tumor-regulating function of CAF are poorly understood. Here, we uncover the Notch1 pathway as a molecular determinant that controls the regulatory role of CAF in melanoma growth, invasion and metastasis, and can be manipulated to reprogram and convert CAF to act as tumor suppressors. The Notch1-determined tumor-regulating function is in part mediated by Wnt-induced secreted protein 1 (WISP1). These findings reveal the Notch1âWISP1 axis as a crucial molecular determinant in governing stromal regulation of tumor progression, and establish this axis as a potential therapeutic target Total RNA obtained from MSCD-SF transduced with Cre-GFP/lentivirus in vitro compared to MSCD-SF transduced with GFP/lentivirus. Samples are duplicates.

2016-05-29 | E-GEOD-65316 | biostudies-arrayexpress

Epigenetic field cancerization in breast cancer using subject-matched tumor, ipsilateral-normal, and contralateral-normal tissues

Project description:Emerging work has demonstrated that histologically normal (non-tumor) tissue adjacent to breast tumor tissue shows evidence of molecular alterations related to tumorigenesis, referred to as field cancerization effects. Although changes in DNA methylation are known to occur early in breast carcinogenesis and the landscape of breast tumor DNA methylation is profoundly altered compared with normal tissue, there have been limited efforts to identify DNA methylation field cancerization effects in histologically normal breast tissue adjacent to tumor. Matched tumor, histologically normal tissue of the ipsilateral breast (ipsilateral-normal), and histologically normal tissue of the contralateral breast (contralateral-normal) were obtained from nine women undergoing bilateral mastectomy. Laser capture microdissection was used to select breast epithelial cells from normal tissues, and neoplastic cells from tumor specimens for genome-scale measures of DNA methylation with the Illumina HumanMethylationEPIC array. We identified substantially more CpG loci that were differentially methylated between contralateral-normal breast and tumor tissue (63,271 CpG loci q < 0.01), than between ipsilateral-normal tissue and tumor (38,346 CpG loci q < 0.01). In addition, we identified differential methylation in ipsilateral-normal relative to contralateral-normal tissue (9,562 CpG loci p < 0.01). Hypomethylated loci in ipsilateral normal relative to contralateral were significantly enriched for breast cancer-relevant transcription factor binding sites including those for ESR1, FoxA1, and GATA3. Hypermethylated loci in ipsilateral-normal relative to contralateral-normal tissue were significantly enriched for CpG island shore regions.

2020-07-10 | GSE133985 | 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