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Impact of short- and long-term extracellular acidosis on gene expression of tumors in vitro and in vivo

ABSTRACT: Impact of short- and long-term extracellular acidosis on gene expression of tumors in vitro and in vivo

PROVIDER: PRJNA682631 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR13200352_1.fastq.gz	Fastqsanger.gz
	SRR13200352_2.fastq.gz	Fastqsanger.gz
	SRR13200353_1.fastq.gz	Fastqsanger.gz
	SRR13200353_2.fastq.gz	Fastqsanger.gz
	SRR13200354_1.fastq.gz	Fastqsanger.gz

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Impact of short- and long-term extracellular acidosis on gene expression of tumors in vitro and in vivo

Project description:Purpose: The aim of the study was to analyze the impact of acidic pHe on gene expression in two experimental tumor lines of the rat in vitro and in vivo. The results of short-term incubation (24 h) were compared to chronically acidosis-adapted cells (5 weeks). Methods: Gene expression was analyzed in AT1 prostate and Walker-256 mammary carcinoma of the rat. Cells were exposed to pH 7.4 and 6.6 for 24 h or 5 weeks. Experimental tumors were implanted in rats and control tumors were compared to tumors in which the glycolytic metabolism was intensified. Results: The analyses revealed that 147 genes were uniformly regulated in both cell lines (in vitro) and 79 genes in both experimental tumors after 24 h at low pH. 265 genes were uniformly regulated during long- and short-term exposure to low pH.

2021-01-02 | GSE162705 | GEO

Extracellular acidosis promotes colonization of lung metastases by mediating extracellular matrix remodeling and vasculogenic mimicry

Project description:Acidosis is a hallmark of the tumor microenvironment caused by the metabolic switch from glucose oxidative phosphorylation to glycolysis. It has been largely associated with tumor growth and progression, nevertheless, how acidosis promotes metastatic dissemination remains largely unknown. In this study, we established a long-term acidosis model using patient-derived lung cancer cells. By comparing xenograft inoculates at the cluster sizes of lung cancer circulating tumor cells, the acidosis cells display significantly higher incidence of secondary tumor establishment than their neutral pH counterparts. Transcriptomics analyses reveal a profound remodeling of the extracellular matrix in the acidosis cells, featuring the upregulation of ITGA4 and HAS3 genes, In clinical specimen, overexpression of both ITGA4 and HAS3 proteins are associated with primary tumors with metastatic ability, and their distribution is markedly accentuated around vascular mimicry structures in secondary tumors. We show that acidosis cells display higher ability of vascular mimicry in vitro, and are enriched in ABC transporter-dependent side population cells. Our data support that acidosis drives tumor metastatic colonization via enhanced extracellular matrix remodeling and vascular mimicry. Assessment on the prognostic value of tumor acidosis for metastasis and possible treatment directions are discussed.

2023-05-21 | GSE200546 | GEO

Extracellular-acidosis restricts one-carbon metabolism and preserves T cell stemness: RNA-seq

Project description:The accumulation of acidic metabolic waste products within the tumor microenvironment profoundly inhibits effector functions of tumor-infiltrating lymphocytes (TILs). However, it is unclear whether extracellular-acidosis impacts T cell metabolic fitness and differentiation status. Here, we surprisingly found that prolonged acid exposure reprogrammed T cell intracellular metabolism and mitochondrial fitness, and preserved T cell stemness. Elevated extracellular-acidosis impaired methionine uptake and metabolism via downregulating SLC7A5, therefore altering H3K27me3 deposition at the promoters of crucial T cell stemness genes. These changes promoted the maintenance of a “stem-like memory” state and improved long-term in vivo persistence and anti-tumor efficacy. Our findings not only reveal the unexpected roles of extracellular-acidosis in the maintenance of stem-like properties of T cells, but also advance our understanding of the direct involvement of methionine metabolism in T cell stemness.

2022-12-05 | GSE216622 | GEO

Extracellular-acidosis restricts one-carbon metabolism and preserves T cell stemness: CUT&Tag

2022-12-05 | GSE216621 | GEO

Analysis of the impact of extracellular acidosis on the expression of miRNAs in experimental tumor lines LLC-WRC 256 and R-3327-AT-1 of the rat

Project description:Hypoxia has been shown to regulate the miRNA expression in tumors. Since many tumors show a extracellular acidosis the aim of the study was to analyze whether the extracellular pH has an impact on the miRNA expression in experimental tumor cells of the rat. Therefore R3327-AT1 Dunning prostate carcinoma and Walker-256 mammary carcinoma cells were incubated at pH 7.4 and 6.6 for 24 and the miRNA expression was analyzed by NGS.

2023-11-29 | E-MTAB-6600 | biostudies-arrayexpress

Extracellular-acidosis restricts one-carbon metabolism and preserves T cell stemness

2023-01-17 | MTBLS6661 | MetaboLights

Extracellular-acidosis restricts one-carbon metabolism and preserves T cell stemness (RNA-seq of sodium lactate samples)

2022-12-05 | GSE219257 | GEO

Impact of chronic extracellular acidosis on gene expression in mammary and pancreatic cancer cell lines

Project description:The study aim was to determine whether the microenvironmental acidosis in solid tumors contributes to cancer aggressiveness via changes in gene expression. RNA seq was carried out in parallel to a large array of phenotypical analyses of proliferation, growth, and invasiveness.

2020-06-13 | GSE152345 | GEO

Next Generation Sequencing of Acidosis Response in Intestinal Epithelial Cells

Project description:Purpose: The goal of this study is to define the impact of extracellular acidosis on transcriptional regulation in intestinal epithelial cells. We identify a significant induction of CREB target genes and upregulation of several genes associated with MAPK signaling. This work provides a frame work for the identification of acidosis signaling pathway in intestinal epithelial cells

2021-05-10 | GSE154982 | GEO

Extracellular acidosis promotes colonization of lung metastases by mediating extracellular matrix remodeling and vasculogenic mimicry

Project description:Extracellular acidosis promotes colonization of lung metastases by mediating extracellular matrix remodeling and vasculogenic mimicry

| PRJNA825255 | ENA

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