PAF receptor in Tumor Repopulation induced by Radiotherapy

• Grant number: 17/08904-7
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: September 01, 2017
• End date: August 31, 2021
• Field of knowledge: Biological Sciences - Immunology - Applied Immunology
• Principal Investigator: Sônia Jancar
• Grantee: Ildefonso Alves da Silva Junior
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated scholarship(s): 19/16281-5 - Molecular mechanisms of PAF/PAFR axis in tumor repopulation after radiotherapy, BE.EP.PD

Abstract

Radiotherapy represents an effective method to control cancer locally. But radiation has an important side effect, which is the possibility of inducing the phenomenon of tumor repopulation, where radio-resistant-tumor cells enter an exacerbated proliferation cycle, causing tumor recurrence in a way more aggressive and resistant to therapeutic resources. Recent evidence suggests the involvement of the lipid mediator "Platelet Activating Factor" (PAF) in this phenomenon. PAF acts on a G protein-coupled receptor (PAFR), expressed by tumor cells and tumor-associated macrophages. It has been shown that irradiation leads to the generation of a series of oxidized phospholipids, which act as PAFR agonists in the tumor microenvironment. It is known that activation of PAFR induces survival and proliferation of tumor cells. In addition, PAFR activation in macrophages reprogrammed these cells to a pro-tumorigenic profile. Thus, our hypothesis will be to evaluate whether ligands of PAFR produced in the irradiated tumor microenvironment contribute to the tumor repopulation phenomenon through the activation of PAFR in both tumor cells and macrophages. This hypothesis will be investigated an innovative model of tumor spheroid (3D) using human tumor cells.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

DA SILVA-JUNIOR, ILDEFONSO ALVES; DALMASO, BARBARA; HERBSTER, SUELLEN; LEPIQUE, ANA PAULA; JANCAR, SONIA. Platelet-activating Factor receptor ligands Protect Tumor cells from radiation-induced cell Death. FRONTIERS IN ONCOLOGY, v. 8, FEB 5 2018. (17/08904-7)