Metastatic signature for Ewing’s sarcoma
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ABSTRACT:
PROVIDER: PRJNA1032106 | ENA |
REPOSITORIES: ENA
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Project description:Ewing’s sarcoma is highly malignant bone tumor that involves childhood and adolescent, and its nature has not been well understood. To clarify its cellular origin and the mechanisms of tumorigenesis, we used ex vivo approach to create a murine model for Ewing’s sarcoma. The osteochondrogenic progenitors derived from the facial zone (FZ) of murine long bones at late gestation were purified by microdissection, introduced with EWS-FLI1 or EWS-ERG retroviruses and transplanted into nude mice. Ewing’s sarcoma-like small round cell sarcoma developed at 100% penetrance, whereas tumor induction was less effective when growth place (GP)-derived cells were used. The different response of gene expression to EWS-FLI1 between FZ and GP cells suggests importance of the specific cellular context for EWS-FLI1 to induce Ewing’s sarcoma. The Wnt/β-catenin pathway was involved in close relationship to the cellular context, with Dkk2 and Wipf1 as important downstream modulators. Furthermore, gene expression profiling revealed similarity between our models and human Ewing’s sarcoma. These results indicate that Ewing’s sarcoma originates from the embryonic osteochondrogenic progenitor.
2014-06-30 | GSE32615 | GEO
Project description:Ewing’s sarcoma (ES) is a highly aggressive bone tumor, and the second most prevalent pediatric bone malignancy. The presence of metastasis at diagnosis decreases the three-year survival rate to 20% and contributes to diminished prognosis. Researches are indispensable for the early characterization of the disease and prediction of metastatic-prone patients, through biomarkers identification. Moreover, there is currently no available data on ES utilizing non-biopsy samples, such as plasma. This study utilizes a proteomic analysis of Ewing's sarcoma patient’s plasma samples and biopsies. Initially, the ES group was compared with the control counterpart. In a next step, the ES arm was further stratified into either initially metastatic and non-metastatic, or poor and good chemotherapy responder groups to identify protein expression profiles that can predict metastatic proneness and chemotherapy response, respectively.
2023-12-19 | PXD035812 | Pride
Project description:Poly(ADP-ribose) polymerase 1 (PARP1) critically facilitates DNA damage response (DDR) that suppresses genomic instability. However, the physiological function of PARP1 in regulating genomic integrity is unclear. We investigated the Ewing’s sarcoma breakpoint region 1 (EWS) and found that it regulated the physiological function of PARP1. EWS was indispensable to dissociation of PARP1 from damaged DNA, promoting DDR and regulating DDR protein expression. Abnormal PARP1 accumulation due to EWS expression silencing, induced hyper-PARylation, which exhausted cellular NAD+ levels and caused cell death in in vitro and in vivo. Positively charged EWS arginine-glycine-glycine (Arg-Gly-Gly, RGG) domains directly interact with poly ADP-ribose (PAR) chains produced by PARP1 and are essential to dissociate PARP1 from damaged DNA. Consistently, Ewing’s sarcoma cells with defective EWS function accumulated PARP1 on chromatin and tissues from Ewing’s sarcoma patients, exhibiting high PARylation levels. Taken together, loss of EWS causes defects in PARP1 dissociation and results in genomic instability.
2020-11-03 | PXD016145 | Pride
Project description:Ewing sarcoma (ES) is the second most common bone tumor affecting children and young adults, with dismal outcomes for patients with metastasis at diagnosis. Mechanisms leading to metastasis remain poorly understood. To deepen our knowledge on ES progression, we have profiled tumors and metastases from a spontaneous metastasis 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. Phenotypical validation of two of these targets, CREB1 and LOXHD1, showed an association with migration and clonogenicity ability. Moreover, previously described CREB1 targets were present amongst the metastatic-enriched results. Combining the different omics datasets, we identified targets as FGD4 that interconnect the different ES biological layers (RNA, protein and methylation status) and are associated to clinical outcome. Further studies will provide insight into ES metastasis mechanisms and ultimately improve survival rates for ES patients.
2025-02-04 | GSE246220 | GEO
Project description:Illumina RNA-Seq will be performed on four Ewing’s sarcoma cell lines and two control cell lines. RNA was extracted from all the lines using a basic Trizol extraction protocol.
2013-01-30 | E-ERAD-144 | biostudies-arrayexpress
Project description:RNA-Seq of Metastatic Clone versus Non-Metastatic Clone in Sarcoma
| PRJNA485780 | ENA
Project description:We report that metastasis in an autochthonous mouse model of sarcoma is driven by a single clone in the primary tumor. We performed RNA-seq comparing the gene expression profiles of the metastatic clones (MC) to matched non-metastatic clones (non-MC) from the same tumor for multiple tumors. RNA from lung metastases (Lung-Met) of matched tumors are sequenced as well.
2019-09-03 | GSE118489 | GEO
Project description:A model of tumor metastasis based on v-src transformed immortalized cell lines was developed. The model consists of highly metastatic PR9692 cell line and a derived clone PR9692-E9 which has lost the metastatic abilities. Introduction of exogenous EGR1 gene into the non-metastasizing PR9692-E9 cells completely restores the metastatic potential. Revealed changes in gene expression provide insight into the molecular mechanisms contolling metastatic behavior of sarcoma cells. Comparison of expression profiles obtained from highly metastatic PR9692 cell line, derived non-metastatic clone PR9692-E9 and non-metastatic PR9692-E9 cells infected with replication-defective retroviral vector SFCVneo-EGR1 containing full length cDNA of EGR1. For each condition three biological replicates were analyzed.
2010-04-06 | E-GEOD-15141 | biostudies-arrayexpress
Project description:A model of tumor metastasis based on v-src transformed immortalized cell lines was developed. The model consists of highly metastatic PR9692 cell line and a derived clone PR9692-E9 which has lost the metastatic abilities. Introduction of exogenous EGR1 gene into the non-metastasizing PR9692-E9 cells completely restores the metastatic potential. Revealed changes in gene expression provide insight into the molecular mechanisms contolling metastatic behavior of sarcoma cells.
2010-03-05 | GSE15141 | GEO
Project description:Exosomes are small RNA and protein containing vesicles that can mediate hetero- and homotypic intercellular communication between normal and malignant cells. Especially, tumor-derived exosomes are believed to mediate reprogramming of the tumor-associated stroma to favor tumor growth and metastasis. In this study we isolated exosomes from three different Ewing’s sarcoma (ES) cell lines by ultracentrifugation. Microarray analysis of ES-derived exosomes and their parental cells was performed to gain insight into the spectrum of transcripts they contain and the functions in which these transcripts might be involved in. In total we analyzed six different samples consisting of three pairs of exosomal and cellular RNA of different Ewing's sarcoma cell lines.
2013-05-01 | E-GEOD-42282 | biostudies-arrayexpress