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Persistent inflammatory stimulation drives the transition of MSCs to inflammatory CAFs that promote pro-metastatic characteristics in breast cancer cells

ABSTRACT: Persistent inflammatory stimulation drives the transition of MSCs to inflammatory CAFs that promote pro-metastatic characteristics in breast cancer cells

PROVIDER: PRJNA679307 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR13081940.fastq.gz	Fastqsanger.gz
	SRR13081941.fastq.gz	Fastqsanger.gz
	SRR13081942.fastq.gz	Fastqsanger.gz
	SRR13081943.fastq.gz	Fastqsanger.gz
	SRR13081944.fastq.gz	Fastqsanger.gz

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Similar Datasets

Persistent inflammatory stimulation drives the transition of MSCs to inflammatory CAFs that promote pro-metastatic characteristics in breast cancer cells

Project description:The pro-inflammatory cytokines tumor necrosis factor α (TNFα) and interleukin 1β (IL-1β) are expressed simultaneously and have tumor-promoting roles in breast cancer. In parallel, mesenchymal stem cells (MSCs) undergo transition at the tumor site to cancer-associated fibroblasts (CAFs), which are generally connected to enhanced tumor progression. Here, we determined the impact of consistent inflammatory stimulation on stromal cell plasticity. MSCs that were persistently stimulated by TNFα+IL-1β (2-3 weeks) gained a CAF-like morphology, accompanied by prominent changes in gene expression, including in stroma/fibroblast-related genes. These CAF-like cells expressed elevated levels of vimentin and fibroblast activation protein (FAP) and demonstrated significantly increased ability to contract collagen gels. Moreover, they have gained the phenotype of inflammatory CAFs, as indicated by reduced expression of α smooth muscle actin (αSMA), increased proliferation and elevated expression of inflammatory genes and proteins, primarily inflammatory chemokines. These inflammatory CAFs released factors that enhanced tumor cell detachment, spreading and migration; the inflammatory CAF-derived factors elevated cancer cell migration by stimulating the chemokine receptors CCR2, CCR5 and CXCR1/2 and Ras-activating receptors, expressed by the cancer cells. Together, these novel findings demonstrate that chronic inflammation, per se, can induce MSC-to-CAF transition, leading to generation of tumor-promoting inflammatory CAFs.

2021-08-10 | PXD022635 | Pride

Persistent inflammatory stimulation drives the transition of MSCs to inflammatory CAFs that promote pro-metastatic characteristics in breast cancer cells [II]

2021-04-20 | GSE161761 | GEO

Persistent inflammatory stimulation drives the transition of MSCs to inflammatory CAFs that promote pro-metastatic characteristics in breast cancer cells [I]

2021-04-20 | GSE161760 | GEO

Persistent inflammatory stimulation drives the transition of MSCs to inflammatory CAFs that promote pro-metastatic characteristics in breast cancer cells [I]

Project description:Persistent inflammatory stimulation drives the transition of MSCs to inflammatory CAFs that promote pro-metastatic characteristics in breast cancer cells [I]

| PRJNA679309 | ENA

Persistent inflammatory stimulation drives the transition of MSCs to inflammatory CAFs that promote pro-metastatic characteristics in breast cancer cells [II]

Project description:Persistent inflammatory stimulation drives the transition of MSCs to inflammatory CAFs that promote pro-metastatic characteristics in breast cancer cells [II]

| PRJNA679308 | ENA

Persistent Inflammatory Stimulation Drives the Conversion of MSCs to Inflammatory CAFs That Promote Pro-Metastatic Characteristics in Breast Cancer Cells.

Project description:The pro-inflammatory cytokines tumor necrosis factor α (TNFα) and interleukin 1β (IL-1β) are expressed simultaneously and have tumor-promoting roles in breast cancer. In parallel, mesenchymal stem cells (MSCs) undergo conversion at the tumor site to cancer-associated fibroblasts (CAFs), which are generally connected to enhanced tumor progression. Here, we determined the impact of consistent inflammatory stimulation on stromal cell plasticity. MSCs that were persistently stimulated by TNFα + IL-1β (generally 14-18 days) gained a CAF-like morphology, accompanied by prominent changes in gene expression, including in stroma/fibroblast-related genes. These CAF-like cells expressed elevated levels of vimentin and fibroblast activation protein (FAP) and demonstrated significantly increased abilities to contract collagen gels. Moreover, they gained the phenotype of inflammatory CAFs, as indicated by the reduced expression of α smooth muscle actin (αSMA), increased proliferation, and elevated expression of inflammatory genes and proteins, primarily inflammatory chemokines. These inflammatory CAFs released factors that enhanced tumor cell dispersion, scattering, and migration; the inflammatory CAF-derived factors elevated cancer cell migration by stimulating the chemokine receptors CCR2, CCR5, and CXCR1/2 and Ras-activating receptors, expressed by the cancer cells. Together, these novel findings demonstrate that chronic inflammation can induce MSC-to-CAF conversion, leading to the generation of tumor-promoting inflammatory CAFs.

| S-EPMC8004890 | biostudies-literature

Next Generation Sequencing Facilitates Quantitative Analysis of EG7-CAFs and MSCs Transcriptomes

Project description:Purpose: The goals of this study are to compare EG7 - CAFs (cancer-associated fibroblasts) and MSCs (mesenchymal stem cells) transcriptome profiling (RNA-seq) generated from Next-generation Sequencing (NGS) to perform optimal high-throughput data analysis Methods: mRNA profiles of CAFs were purified from EG7 tumor bearing mice and early passage (p6) murine MSCs purchased from Cyagen were cultured in DMEM for no more than 2 passages were generated by deep sequencing, in triplicate, using Illumina HiSeq 3000. The sequence reads that passed quality filters were analyzed at the transcript isoform level TopHat followed by Cufflinks Results: Comparative high throughput RNA-sequencing (seq) analysis of purified EG7-CAFs and the early passage murine MSCs, which are thought to be precursors for some CAFs and used as the control for normal mesenchymal cells, by using an optimized data analysis workflow, we mapped about 50 million sequence reads per sample to the mouse genome (build mm10) and identified 11,839 transcripts with TopHat workflow. Approximately 1584 of the transcripts showed differential expression between the EG7 - CAFs and MSCs, with a fold change ≥ 2 and p value <0.01 Conclusions: Our results clearly support the notion that CAFs are transcriptionally different from MSCs in various pathways and biological processes associated with immune modulation, inflammation, hypoxia, and activation of oncogenic pathways

2019-11-30 | GSE141199 | GEO

Persistent inflammatory stimulation drives the transition of MSCs to inflammatory CAFs that promote pro-metastatic characteristics in breast cancer cells

Project description:This SuperSeries is composed of the SubSeries listed below.

2021-04-20 | GSE161762 | GEO

Next Generation Sequencing Facilitates Quantitative Analysis of EG7-CAFs and MSCs Transcriptomes

Project description:Next Generation Sequencing Facilitates Quantitative Analysis of EG7-CAFs and MSCs Transcriptomes

| PRJNA592566 | ENA

The microarray gene expression analysis was performed between inflammatory serum or inactive serum stimulated hUC-MSCs

Project description:Peripheral infusion of human umbilical cord mesenchymal stem cells (hUC-MSCs) can profoundly suppress the activation of c-Mos and remarkably improve hepatic histology, suppress the systemic inflammatory reaction, and promote animal survival in a large non-human primate model of acute liver failure (ALF). The mechanism through which hUC-MSCs inhibits c-Mos activation in vivo remains unclear. We hypothesized that hUC-MSCs can adaptively produce certain inhibitory cytokines in response to the pro-inflammatory microenvironment. To confirm this, we stimulated cultured hUC-MSCs with inflammatory monkey serum (serum isolated at day 1 following toxin challenge). After a 30-min stimulation, the cells were collected for microarray gene expression analysis. A whole human genome oligo microarray analysis was performed to reveal the altered gene expression profiles of the hUC-MSCs

2016-05-12 | E-MTAB-4750 | biostudies-arrayexpress

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