Project description:Vanin1, a regulator of vitamin B5 metabolism, is expressed by sarcoma tumors. We evaluated its impact on sarcoma growth by using sarcoma cell lines derived from p16p19Vnn1-deficient mice and further transduced with an oncogenic RasV12 oncogene (R tumors) in the presence or not of a catalytically active (VR tumors) or mutated (VdR tumors) Vnn1 isoform. We used microarrays to detail the global programme of gene expression associated with the growth potential of various tumor cell lines grafted in Nude mice
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.
Project description:As a high-grade soft-tissue sarcoma (STS), undifferentiated pleomorphic sarcoma (UPS) is highly recurrent and malignant. UPS is categorized as “tumor of uncertain differentiation” and few options for treatment resulting from lack of targetable genetic alterations. There are also few cell lines representative subtype for UPS, leading to poor experimental evidence. Here, we have established and characterized new cell lines derived from recurrent two UPS tissues. Cells were obtained UPS tissues by mincing followed by extracting or dissociating using enzymes and cultured by regular culture environment. Cells were maintained and immortal for months without artificial treatment and some cell clones were tumorigenic in immunodeficient mouse model. Interestingly, some cells formed tumor in vivo when injected after aggregation in non-adherent culture system for 24 h. The tissues from in vivo study and tissues from patients were compared if it is representative for UPS by immunohistochemistry. Pathways related to cell cycle as DNA replication were common between cell clones while cell clones, tumorigenic in regardless of aggregation for injection, were increased expression of pathways related to cell-cell adhesion, as well as cell-cell signaling, implying a role of mesenchymal to epithelial transition for tumorigenicity in vivo. This study showed that new UPS cell lines might be a good resource for UPS study to get new insights leading to better therapeutic strategy against UPS.
Project description:Background: Sarcoma oncogenesis is still poorly understood and there is a pressing need to generate cell lines representative of diverse sarcoma types. Methods: We submitted to culture all sarcoma from patients receiving surgery in a large tertiary referral centre in France. Of the 32 established cell lines we report the genomic and transcriptomic study of 7 which were extensively tested for the representativeness to the original tumor and the evolution over passages. Results: Pleomorphic sarcomas are genetically heterogeneous. As a consequence, cell lines derived from that kind of tumor developed from selected clones roughly representing the initial tumor. More importantly our results show that there are no genetic imbalances and transcription modifications along passages. Conclusions: This likely means that even if pleomorphic sarcomas are genetically unstable at the cellular level, they appear to be genetically stable at the multicellular one and therefore remain representative of the initial tumor even after passages. We established a sarcoma cell line panel gathering 32 cell lines with genomic, transcriptomic and clinical data, which will be very powerful to go further in the understanding of genomic alterations, sarcoma biology and to manage preclinical studies and clinical trials.
Project description:Ewing sarcoma a rare pediatric tumor characterized by EWSR1-ETS fusions. We performed expression profiling of both miRNA and mRNA from the same Ewing's sarcoma tumors. We propose a novel statistical measure of non-linear dependence between miRNA and mRNA expression, In order to infer miRNA-target interactions. This approach, That we name antagonism pattern detection, Is based on the statistical recognition of a triangular-shaped pattern in miRNA-target expression profiles. This pattern is observed in miRNA-target expression measurements since their simultaneously elevated expression is statistically under-represented in the case of miRNA silencing effect. The proposed method enables miRNA target prediction to strongly rely on cellular context and physiological conditions reflected by expression data. Expression profiling of Ewing sarcoma samples in the frame of the CIT program from the french Ligue Nationale Contre le Cancer (http://cit.ligue-cancer.net). Total RNAs issued of 39 Ewing tumors were used for mRNA and miRNA microarray analyses. The mRNA data were collected using the Affymetrix GeneChip HG-U133A and Affymetrix GeneChip HG-U133Plus2.
Project description:This SuperSeries is composed of the following subset Series: GSE37370: microRNA expression data from Ewing's sarcoma tumor samples GSE37371: Expression data from Ewing's sarcoma tumor samples Refer to individual Series