Whole-organ analysis of TGF-b-mediated remodelling of the tumour microenvironment
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA642788 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR12107319.fastq.gz | Fastqsanger.gz | |||
| SRR12107320.fastq.gz | Fastqsanger.gz | |||
| SRR12107321.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 3 of 3 |
Similar Datasets
Project description:Tissue clearing technique may be one of the most powerful strategies for a comprehensive and unbiased analysis of disease progression. Here, we improved a tissue clearing protocol and explored its application in a mouse tumour model of experimental lung metastasis. We established an integrated pipeline for 3D profiling of the tumour microenvironment in combination with our new clearing protocol and machine learning. This pipeline distinguished each cellular component within the tumour microenvironment, and provided information on their spatial relationships. We further explored the role of TGF-b in the tumour microenvironment using this integrated pipeline. TGF-b-stimulated cancer cells enhanced metastatic colonization of unstimulated-cancer cells in vivo when both cells were mixed. RNA-sequencing analysis showed that expression of the genes related to coagulation and inflammation were up-regulated in TGF-b-stimulated cancer cells. Further, 3D profiling of the tumour microenvironments revealed accumulation of platelets or macrophages with TGF-b-stimulated cancer cells, suggesting that TGF-b might promote remodelling of the tumour microenvironment through the activation of these cellular components at the metastatic sites, which further enhances the colonization of cancer cells. Hence, an integrated pipeline that combines tissue clearing, 3D imaging, and machine learning will help further the understanding of the role of the tumour microenvironment.
2021-03-10 | GSE153468 | GEO
Project description: Not available
| S-EPMC7935961 | biostudies-literature
Project description:Interactions between mutant cells and their environment play a key role in determining cancer susceptibility. However, our understanding of how the pre-cancerous microenvironment contributes to early tumorigenesis remains limited. Here, we show that newly emerging tumours at their most incipient stages shape their microenvironment in a critical process that determines their survival. Analysis of nascent squamous tumours in the upper gastrointestinal tract of the mouse reveals that the stress response of early tumour cells instructs the underlying mesenchyme to form a supportive “pre-cancerous niche”, which dictates the long-term outcome of epithelial lesions. Stimulated fibroblasts beneath emerging tumours activate a wound healing response that triggers a dramatic remodelling of the underlying extracellular matrix, resulting in the formation of a fibronectin-rich stromal scaffold that promotes tumour growth. Functional heterotypic 3D culture assays and in vivo grafting experiments, combining carcinogen-free healthy epithelium and tumour derived stroma, demonstrate that the pre-cancerous niche alone is sufficient to confer tumour properties to normal epithelial cells. We propose a model where both mutations and the stromal response to genetic stress together define the likelihood of early tumours to persist and progress towards more advanced disease stages.
2025-12-23 | GSE271962 | GEO
Project description:Pre-cancerous Niche Remodelling Dictates Nascent Tumour Persistence
| PRJNA1134210 | ENA
Project description:Organ-Specific Transcriptional and Metabolic Remodelling During Late Mouse Adolescence
| PRJNA1490470 | ENA
Project description:Extracellular pH (pHe) is lower in many tumors than in the corresponding normal tissue. Acidic tumor microenvironment has been shown to facilitate epithelial mesenchymal transition (EMT) and tumor metastasis, while the mechanisms underlying tumor acidic microenvironment-induced tumor cell metastasis remain undefined. Here, we aimed to investigate the tumor metastasis and the EMT by acidic microenvironment and to explore their mechanisms and clinical significance in lung cancer. Results showed that acidic pHe remarkably enhanced invasion ability of lung cells accompanying with increased mesenchymal and decreased epithelial markers. Moreover, acidic pHe triggered the inhibition of microRNA-7 (miR-7) expression and activation of TGF-β2/SMAD signaling. Mechanistic studies showed that TGF-β2 is a direct potential target gene of miR-7, and acidity-induced metastasis could be abolished by treatment with a TGFβRI inhibitor, anti-TGF-β2 antibody and miR-7 mimic, respectively. The clinical samples further revealed that miR-7 was decreased in lung tissues and antagonistically correlated with TGF-β2 expression, associating with overall survival and metastasis. In conclusion, our study indicated that acidic pHe showed enhanced invasive potential, and enhanced potential to develop experimental metastases by a novel mechanism involving tumor acidic microenvironment-induced regulation of miR-7/TGF-β2/SMAD axis. Our findings suggest that the possibility that pHe of the primary tumor may be an important prognostic parameter for lung cancer patients merit clinical investigation. Moreover, miR-7 may serve as prognostic molecular marker and a novel therapeutic target for lung cancer.
2022-04-01 | PXD016524 | Pride
Project description:Remodelling of the immune landscape by IFNγ counteracts IFNγ-dependent tumour escape in mouse tumour models
| PRJNA1084756 | ENA
Project description:Cancer associated fibroblasts characterized by an myofibroblastic phenotype play a major role in the tumour microenvironment, being associated with poor prognosis. We found that this cell population is made in part by senescent fibroblasts in vivo. As senescent fibroblasts and myofibroblasts have been shown to share similar tumour promoting functions in vitro we compared the transcriptosomes of these two fibroblast types and performed RNA-seq of human foetal foreskin fibroblasts 2 (HFFF2) treated with 2ng/ml TGF-beta-1 to induce myofibroblast differentiation or 10Gy gamma irradiation to induce senescence. We isolated RNA 7 days upon this treatments changing the medium 3 days before the RNA extraction. A series of SAM alignment files (named after the sample names, for simplicity) are available under http://www.ebi.ac.uk/arrayexpress/experiments/E-MTAB-3101/files/ .
2017-06-01 | E-MTAB-3101 | biostudies-arrayexpress
Project description:Prostate carcinoma is the most common malignancy in males and the second leading cause of cancer-related deaths in Western countries. Loss of the tumour suppressor PTEN, encoded by one of the most frequently deleted genes in human prostate cancer, is associated with a highly immunosuppressive tumour microenvironment (TME). In consequence, immunotherapies targeting prostate cancer typically show low clinical efficacy. The immunosuppressive TME state is mediated in part by various cytokines and chemokines resulting in infiltration of heterogeneously differentiated myeloid cells including polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs). Here we show that the methyltransferase KMT9 regulates expression of immunosuppressive proteins such as PD-L1 and myeloid-attracting CXCR2 ligands in prostate tumours of Pten/Trp53 knockout (KO) mice. Accordingly, KMT9 ablation in Pten/Trp53 KO tumours results in chemokine downregulation and TME remodelling towards an immunoresponsive state characterised by an altered composition and spatial distribution of PMN-MDSCs and other immune cell populations. Importantly, combining KMT9 deficiency with CXCR2 inhibition blocks myeloid cell recruitment resulting in prostate tumour regression and extended mouse survival. Together, our findings uncover KMT9 as a TME regulator and pave the way for the development of novel immunotherapeutic approaches for the treatment of prostate cancer.
2026-09-23 | GSE253017 | GEO
Project description:Prostate carcinoma is the most common malignancy in males and the second leading cause of cancer-related deaths in Western countries. Loss of the tumour suppressor PTEN, encoded by one of the most frequently deleted genes in human prostate cancer, is associated with a highly immunosuppressive tumour microenvironment (TME). In consequence, immunotherapies targeting prostate cancer typically show low clinical efficacy. The immunosuppressive TME state is mediated in part by various cytokines and chemokines resulting in infiltration of heterogeneously differentiated myeloid cells including polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs). Here we show that the methyltransferase KMT9 regulates expression of immunosuppressive proteins such as PD-L1 and myeloid-attracting CXCR2 ligands in prostate tumours of Pten/Trp53 knockout (KO) mice. Accordingly, KMT9 ablation in Pten/Trp53 KO tumours results in chemokine downregulation and TME remodelling towards an immunoresponsive state characterised by an altered composition and spatial distribution of PMN-MDSCs and other immune cell populations. Importantly, combining KMT9 deficiency with CXCR2 inhibition blocks myeloid cell recruitment resulting in prostate tumour regression and extended mouse survival. Together, our findings uncover KMT9 as a TME regulator and pave the way for the development of novel immunotherapeutic approaches for the treatment of prostate cancer.
2026-09-23 | GSE252976 | GEO