IP: Dr. Enrique de Álava

Resumen del proyecto: Bone marrow-derived human mesenchymal stem cells (hMSCs), which are classic mesodermal derivatives, express an extensive assortment of neural genes, and therefore, are predisposed to differentiate to neural and glial lineages (Blondheim et al., 2006). Considering the neural features of Ewing’s sarcoma (ES) and the bone and soft tissue localization, hMSCs seem to be excellent candidates susceptible of EWS-FLI1 transformation and initiation of ES. In fact, the development of ES from primary BM-derived mesenchymal cells has been already described in mice (Riggi et al., 2005) and the profiles of different EWS-FLI1-silenced Ewing cell lines converge toward that of mesenchymal stem cells (Tirode et al., 2007). Recently, Riggi et al (2008) disclosed that EWS-FLI-1 expression in hMSCs from patients recapitulated the early events in ES initiation program, although additional events are required to form a tumor in immunocompromised mice. In order to unravel the early signaling events involved in sarcomagenesis and to characterize the cancer stem cell population responsible of tumor relapse for a possible therapy, several strategies will be performed: - Generation of a cellular model of hMSC with inducible expression of most prevalent gene fusions of ES in order to characterize cell signaling pathways involved in ES sarcomagenesis. - Identification of signalling pathways relevant for cell renewal in ES cancer stem cells.

Entidad financiadora: Instituto de Salud Carlos III