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Mediators of Inflammation
Volume 2012 (2012), Article ID 610371, 6 pages
http://dx.doi.org/10.1155/2012/610371
Research Article

Apoptotic Cells Contribute to Melanoma Progression and This Effect is Partially Mediated by the Platelet-Activating Factor Receptor

1Microbiology, Immunology, and Parasitology Department, Federal University of São Paulo, 04023-900 São Paulo, SP, Brazil
2Pathology Division, Adolfo Lutz Institute, 01246-000 São Paulo, Brazil
3Immunology Department, University of São Paulo, 05508-900 São Paulo, SP, Brazil
4Pharmacology Department, Federal University of São Paulo, 04023-032 São Paulo, SP, Brazil

Received 1 October 2011; Accepted 1 February 2012

Academic Editor: M. Sanchez Crespo

Copyright © 2012 André Luis Lacerda Bachi et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

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.