Angiogec potential of PAF receptor ligands in irradiated tumors

Abstract

Recent evidence suggests the participation of the lipid mediator "Platelet Activating Factor" (PAF) in tumor growth and resistance to chemo-radiotherapy. PAF acts through a G protein-coupled receptor (PAFR), expressed on tumor cells and also on the tumoral infiltrate cells. It has been shown that irradiation leads to the generation of a series of oxidized phospholipids that act as PAFR agonists in the tumor microenvironment. The activation of PAFR induces survival and proliferation of tumor cells. Preliminary results from our group showed that subcutaneous injection of tumor cells expressing the PAF receptor (PAFR +) generate significantly larger and more vascularized tumors than negative PAFR tumors, suggesting the participation of PAF as a pro-angiogenic factor. Thus, understanding the signals that regulate tumor angiogenesis is fundamental for the development of new therapeutic alternatives. Thus, our work hypothesis aims to evaluate whether ligands of PAFR produced in the irradiated tumor microenvironment contribute to tumor angiogenesis, amplifying the phenomenon of tumor repopulation after irradiation. This hypothesis will be investigated in an innovative model of tumor spheroid (3D) using human tumor cells. (AU)