There is evidence that the
platelet-activating factor receptor (PAFR) is involved in the clearance of apoptotic cells by macrophages, and that this is associated with anti-inflammatory phenotype. Our group has previously shown that coinjection of a large number of apoptotic cells can promote
tumor growth from a subtumorigenic dose of
melanoma cells. Here, we studied the involvement of the PAFR in the
tumor growth promoting effect of apoptotic cells. A sub-tumorigenic dose of
melanoma cells (Tm1) was coinjected with apoptotic Tm1 cells, subcutaneously in the flank of C57Bl/6 mice, and the volume was monitored for 30 days. Animals received the PAFR antagonists,
WEB2170 or PCA4248 (5 mg/kg
body weight) or vehicle, by peritumoral daily injection for 5 days. Results showed that PAFR antagonists significantly inhibited the
tumor growth induced by the coinjection of a sub-tumorigenic dose of
melanoma cells together with apoptotic cells. This was accompanied by inhibition of early neutrophil and macrophage infiltration. Addition of (
platelet-activating factor) to this system has no significant effect. PAFR antagonists did not affect the promoting effect of
carrageenan. We suggest that the recognition of apoptotic cells by phagocytes leads to activation of PAFR pathways, resulting in a microenvironment response favorable to
melanoma growth.