Project overview
Ewing’s sarcoma (EwS) is the second most common primary bone sarcoma in people aged 30 and under. The most common underlying cause is the EWS-FLI1 gene fusion, which drives expression of Neuropeptide-Y (NPY). Under normoxic conditions, NPY acts upon Y1/Y5 receptors to activate cell death but in EwS there is tumour hypoxia causing increased expression of dipeptidyl peptidase 4 (DPP-4), which truncates NPY to NPY3-36. Tumour-associated macrophages (TAMs), which have been established as a poor prognostic marker in EwS, may also have a role in DPP-4 and NPY metabolism. This project aim is to determine the expression of NPY, NPY3-36., DPP4, Y1 and Y5 receptors in Ewing’s sarcoma and to test the effect of macrophage-secreted DPP4 upon EwS cells and to attempt to block any pro-tumoral effects with DPP4 inhibitors including gliptins.
