Role of PAF receptor in tumor cells and phenotype of macrophages

Abstract

Several lines of evidence suggest that PAFR-mediated signaling may be involved in tumor growth and macrophage M1/M2 phenotype generation. PAF biological effects are mediated through specific membrane receptor coupled with G-proteins (PAF-R) that is expressed in many cell types, including tumor cells. Recent results from our group demonstrated that some chemotherapeutic drugs can increase the expression of PAFR in tumor and exert a cytoprotective effect, increasing viability of tumor cells. It has also been shown that injection of PAF together with B16F10 murine melanoma cells in mice increased tumor growth. There is evidence that blockade of PAFR may also prevent the establishment of a suppressor phenotype of tumor associated macrophages, however, the mechanisms involved in the activation of PAFR in both, tumor cells and infiltrating inflammatory cells that can participate in the modulation of tumor growth still unclear. This project will investigate the role of PAFR in proliferation of tumor cell lines and in functional and phenotypic modulation of tumor associated macrophages (TAM). The data obtained from this study will help to clarify the function of PAFR in tumor progression and in tumor resistance to chemotherapy. (AU)