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[Cancer Research 63, 3464-3468, July 1, 2003]
© 2003 American Association for Cancer Research

Advances in Brief

Ewing Tumor Fusion Proteins Block the Differentiation of Pluripotent Marrow Stromal Cells1

Enrique C. Torchia, Sobha Jaishankar2 and Suzanne J. Baker3

Department of Developmental Neurobiology, St. Jude Children’s Research Hospital, Memphis, Tennessee

The Ewing family of tumors are poorly differentiated pediatric solid tumorsarising in bone and soft tissues from an unknown cell of origin. Ewingtumors are molecularly defined by in-frame genomic fusions that combine EWS with one of several ETS genes, most commonly FLI-1. We considered pluripotent marrow-derived stromal cells a likely candidate for the origin of Ewing tumors and assessed the effects of EWS/ETS proteins in this cell background. EWS/ETS expression in marrow-derived stromal cells caused a dramatic change in cellular morphology that was dependent on the presence of the ETS domain and unique to the fusion proteins. EWS/ETS fusion proteins blocked differentiation along osteogenic and adipogenic lineages, consistent with the undifferentiated appearance of Ewing tumors. Inhibition of differentiation may be an important function of EWS/ETS proteins in the genesis of Ewing tumors.




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