Expression data of mouse eSZ and GP cells with or without EWS-FLI1

Ewings 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 Ewings 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. Ewings 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 Ewings sarcoma. The Wnt/-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 Ewings sarcoma. These results indicate that Ewings sarcoma originates from the embryonic osteochondrogenic progenitor.

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Tanaka M, Yamazaki Y, Kanno Y, Igarashi K, Aisaki K, Kanno J, Nakamura T