Multi-omics approach to decipher Ewing sarcoma metastases using a spontaneous metastasis mouse model
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PROVIDER: PRJNA1027354 | ENA |
REPOSITORIES: ENA
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Project description:Ewing sarcoma (ES) is the second most common bone tumor affecting children and young adults, with dismal outcomes for patients with metastases at diagnosis. Mechanisms leading to metastasis remain poorly understood. To deepen our knowledge on ES progression, we have profiled 3 tumors and 5 metastases from our spontaneous metastasis ES mouse model using a multi-omics approach. Combining transcriptomics, proteomics and methylomics analyses, we identified signaling cascades and targets enriched in metastases that could be modulating aggressiveness in ES.
2024-12-03 | GSE245203 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE36857: Goldengate Methylation analysis: Ewing Sarcoma GSE36858: 5- AZA treatment of EWS cell lines Refer to individual Series
2012-09-01 | E-GEOD-36859 | biostudies-arrayexpress
Project description:Ewing sarcoma is an aggressive pediatric small round cell tumor that predominantly occurs in bone. Approximately 85% of Ewing sarcomas harbor the EWS/FLI fusion protein, which arises from a chromosomal translocation, t(11:22)(q24:q12). EWS/FLI interacts with numerous lineage-essential transcription factors to maintain mesenchymal progenitors in an undifferentiated state. We previously showed that EWS/FLI binds the osteogenic transcription factor RUNX2 and prevents osteoblast differentiation. In this study, we investigated the role of another Runt-domain protein, RUNX3, in Ewing sarcoma. RUNX3 participates in mesenchymal-derived bone formation and is a context dependent tumor suppressor and oncogene. RUNX3 was detected in all Ewing sarcoma cells examined, whereas RUNX2 was detected in only 73% of specimens. Like RUNX2, RUNX3 binds to EWS/FLI via its Runt domain. EWS/FLI prevented RUNX3 from activating the transcription of a RUNX-responsive reporter, p6OSE2. Stable suppression of RUNX3 expression in the Ewing sarcoma cell line A673 delayed colony growth in anchorage independent soft agar assays and reversed expression of EWS/FLI-responsive genes. These results demonstrate an important role for RUNX3 in Ewing sarcoma. RNA-seq to compare transcriptiome of control A673 ewing sarcoma cells stably expression a non-target or RUNX3 shRNA
2014-05-01 | E-GEOD-56900 | biostudies-arrayexpress
Project description:The expression profile of primary pediatric Ewing sarcoma (ES) and osteosarcoma (OS) were analyzed. 8 Ewing sarcoma patient samples (TUM-ES0XXX) and 10 osteosarcoma patient samples (TUM-OS0XXX) were analyzed.
2016-07-05 | E-GEOD-73166 | biostudies-arrayexpress
Project description:Ewing sarcoma is an aggressive cancer most commonly diagnosed in adolescents and young adults. Various mechanisms of TGFβ inhibition are being tested in clinical trials for patients with relapsed Ewing sarcoma. However, the functional impact of TGFβ inhibition on the Ewing tumor microenvironment remains largely unstudied given the historical lack of immunocompetent preclinical models of Ewing sarcoma. Here, we use single cell RNAseq analysis of human Ewing tumors to demonstrate that immune cells are the largest source of TGFβ production in the human Ewing tumor microenvironment. We develop and utilize a humanized mouse model of Ewing sarcoma to study the effect of TGFβ inhibition on the Ewing tumor immune microenvironment both at baseline and during radiation therapy, a treatment that enhances TGFβ activation and is often used to treat patients with aggressive Ewing sarcoma. Finally, we utilize a bivalent ligand TGFβ TRAP and demonstrate that, in combination with radiation, TGFβ inhibition both increases immune cell infiltration in Ewing tumors and decreases lung metastatic burden.
2025-05-20 | GSE261693 | GEO
Project description:Tumor: tumor microenvironment (TME) interactions are critical for tumor progression and the composition and structure of the local extracellular matrix (ECM) are key determinants of tumor metastasis. We recently reported that activation of Wnt/beta- catenin signaling in Ewing sarcoma cells induces widespread transcriptional changes that are associated with acquisition of a metastatic tumor phenotype. Significantly, ECM protein-encoding genes were found to be enriched among Wnt/beta-catenin induced transcripts, leading us to hypothesize that activation of canonical Wnt signaling might induce changes in the Ewing sarcoma secretome. To address this hypothesis, conditioned media from Ewing sarcoma cell lines cultured in the presence or absence of Wnt3a was collected for proteomic analysis. Label-free mass spectrometry was used to identify and quantify differentially secreted proteins. We then used in silico databases to identify only proteins annotated as secreted. Comparison of the secretomes of two Ewing sarcoma cell lines revealed numerous shared proteins, as well as a degree of heterogeneity, in both basal and Wnt-stimulated conditions. Gene set enrichment analysis of secreted proteins revealed that Wnt stimulation reproducibly resulted in increased secretion of proteins involved in ECM organization, ECM receptor interactions, and collagen formation. In particular, Wnt-stimulated Ewing sarcoma cells upregulated secretion of structural collagens, as well as matricellular proteins, such as the metastasis-associated protein, tenascin C (TNC). Interrogation of published databases confirmed reproducible correlations between Wnt/beta-catenin activation and TNC and COL1A1 expression in patient tumors. In summary, this first study of the Ewing sarcoma secretome reveals that Wnt/beta-catenin activated tumor cells upregulate secretion of ECM proteins. Such Wnt/beta-catenin mediated changes are likely to impact on tumor: TME interactions that contribute to metastatic progression.
2018-02-07 | PXD007909 | Pride
Project description:Study of promoter methylation of ewing sarcoma cell lines and mesenchymal stem cell from ewing sarcoma patients and healthy donors
2018-10-24 | GSE118872 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE17618: Inflammatory gene profiling of Ewing sarcoma family of tumors (set A) GSE17674: Inflammatory gene profiling of Ewing sarcoma family of tumors (set B) Refer to individual Series
2011-12-01 | E-GEOD-17679 | biostudies-arrayexpress
Project description:Primary pediatric Ewing sarcoma (ES), one uncharacterized sarcoma as well as primary and well established ES cell lines were compared to probes of different normal tissues 8 Ewing sarcoma patient samples (MuET-x), 3 primary ES cell lines (SB-KMS-y), 3 well established ES cell lines (A673, SK-N-MC, RD-ES) and 22 normal tissues (PBMC, spleen, thymus, stomach, ...., uterus, fetal brain, fetal liver) were analyzed.
2013-05-01 | E-GEOD-45544 | biostudies-arrayexpress