Ewing tumor fusion proteins block the differentiation of pluripotent marrow stromal cells

EC Torchia, S Jaishankar, SJ Baker - Cancer research, 2003 - AACR
EC Torchia, S Jaishankar, SJ Baker
Cancer research, 2003AACR
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 …
Abstract
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.
AACR