Project name: Mus musculus

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.Overall design: Ewing's sarcoma was induced by introduction of EWS-FLI1 into murine FZ cell followed by transplantation into nude mice. Ten sarcoma samples were analyzed.No controls are part of this experimentFor comparing with human Ewing's sarcoma, we used expression databases E-MEXP-533 (Henderson SR et al, Genome Biol 6:R76, 2005) and E-MEXP-1142 (Schaefer KL et al, Eur J Cancer 44:699, 2008). In addition, the data sets for other sarcomas that include GSE6481 (Nakayama R et al, Mod Pathol 20:749, 2007), GSE7529 (Albino D et al, Cancer 113:1412, 2008) and GSE21122 (Barretina J et al, Nat Genet 42:715, 2010) were used for clustering analysis.

Data type: Transcriptome or Gene expression

Sample scope: Multiisolate

Relevance: ModelOrganism

Last updated: 2011-10-04