Pediatric solid tumor unit

Molecular Oncology
Instituto de Salud Carlos III (ISC III)

Role of matricellular proteins in the development and progression of Ewing sarcoma: prognostic and therapeutic implications

Ewing's sarcoma is the second most common bone tumor in children and adolescents behind osteosarcoma. Although in recent years have been made significant progress in understanding the molecular basis of this disease, mainly in relation to the identification of target genes of the EWS-FLI1 oncoprotein (the molecular hallmark of these tumors), these advances have not been translated in the development of new treatments. In this project we propose to study the role of matricellular proteins, a heterogeneous group of proteins that play key roles in bone homeostasis and in the processes of osteo-chondrogenic differentiation, in the development and progression of Ewing's sarcoma. To this end the following objectives are proposed: 1) Characterize the role of EWS-FLI1 in regulating the matricellular component in vitro and in several in vivo models to determine to what extent the microenvironment influences the expression of target genes; 2) Characterize the function of the matricellular proteins in the development and progression of Ewing's sarcoma, studying its effect on cell differentiation, tumorigenic characteristics and metastatic capacities; and 3) Determine the value of these proteins as markers of progression and response to therapy in a cohort of patients well characterized from the clinical point of view. These studies will allow us to define in detail the role of these proteins in the development of Ewing sarcoma and evaluate their prognostic and therapeutic implications.

Biomolecules & Cell D.
Molecular Biomedicine