Tissue-engineered bone tumor as a reproducible human in vitro model for studies of anti-cancer drugs
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE135323 | GEO | 2020/01/15
REPOSITORIES: GEO
Similar Datasets
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 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 embryonic superficial zone (eSZ, designated as FZ in the data set) 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 eSZ 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 | GSE32618 | GEO
Project description:DNA Methylation-Based Classifier for Accurate Molecular Diagnosis of Bone Sarcomas: DNA methylation status of 482,421 CpG sites in 10 Ewing’s sarcoma, 11 synovial sarcoma, and 15 osteosarcoma samples were determined using the Illumina HumanMethylation450 array.
2017-10-08 | GSE97529 | GEO
Project description:Studies of anticancer therapies in traditional cell culture models can demonstrate efficacy of direct-acting compounds but lack the 3-dimensional arrangement of the tumor cells and their tissue-specific microenvironments, both of which are important modulators of treatment effects in vivo. Bone cells reside in complex environments that regulate their fate and function. A bioengineered human bone-tumor model has been shown to provide a microphysiological niche for studies of cancer cell behavior. Here, we demonstrate successful transfer between 2 laboratories and utility of this model in efficacy studies using well-established chemotherapeutic agents. The bioengineered human bone-tumor model consisted of Ewing sarcoma (RD-ES) cancer cell aggregates infused into tissue-engineered bone that was grown from human mesenchymal stem cell-derived differentiated into osteoblasts within mineralized bone scaffolds. The tumor model was maintained in culture for over 5 weeks and subjected to clinically relevant doses of linsitinib, doxorubicin, cisplatin, methotrexate, vincristine, dexamethasone, or MAP (methotrexate, doxorubicin, and cisplatin combination). Drug administration cycles were designed to mimic clinical treatment regimens. The bioengineered tumors were evaluated days to weeks after the cessation of treatment to monitor the potential for relapse, using bioengineered bone and ES cell monolayers as controls. Drug binding to the scaffolds and media proteins and gene expression were also evaluated. We show that a bioengineered human bone tumor can be used as a microphysiological model for preclinical studies of anticancer drugs. We found that anticancer efficacy was achieved at concentrations approximating the human Cmax, in contrast to traditional ES cell monolayers. These studies show that the bone-tumor model can be successfully transferred between laboratories and has predictive power in preclinical studies. The effects of drugs on the bone tumors and healthy bone were studied in parallel, in support of the utility of this model for identification of new therapeutic targets.
| S-EPMC8204946 | biostudies-literature
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:Tissue-engineered bone tumor as a reproducible human in vitro model for studies of anti-cancer drugs
| PRJNA558389 | ENA
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:Microarray analysis was used to evaluate expression differences from a single donor human bone marrow stromal cells (hBMSCs) as a function of varied polymer-based tissue engineering scaffolds. These scaffolds include polycaprolactone (PCL) nanofibers (PCL_NF), films (PCL_SC), poly D,L-lactic acid (PDLLA) nanofibers (PDLLA_NF), films (PDLLA_SC), tissue culture polystyrene (TCPS) and TCPS with osteogenic supplements (TCPS_OS). The results revealed that scaffold structure was able to significantly affect gene expression, with nanofiber scaffolds inducing similar gene expression patterns to hBMCSs cultured with osteogenic media. A library of scaffolds prepared from polycaprolactone or poly D,L-lactic acid was sythesized and cultured with hBMSCs for 14 days with RNA extracted from cells on Day 1 and Day 14. Gene expression analysis was performed using BRB ArrayTools. SC = spun coat, BNF = big nanofiber, TCPS = tissue culture polystyrene, TCPS+OS = tissue culture polystyrene with osteogenic supplements. This data forms is part of a pending publication: Baker et al. Ontology Analysis of Global Gene Expression Differences of Human Bone Marrow Stromal Cells Cultured on 3D Scaffolds or 2D Films and is a subset of the 72 array data referenced in ( Kumar et al. The determination of stem cell fate by 3D scaffold structures through the control of cell shape, Biomaterials (2011) 32, 9188-9196.) The 72 array data set is submitted separately to GEO as GSE50743.
2013-11-01 | E-GEOD-50744 | biostudies-arrayexpress