PAF receptor and tumor growth.

Abstract

The receptor for the lipid mediator PAF (PAFR) is a G-protein coupled receptor expressed in several cell types. Besides PAF, a series of oxidized phospholipids can also bind to PAFR. Dying cells also express PAFR-ligands and, in both situations, scavenger receptors are involved as well. There is evidence that the scavenger receptor CD36 and PAFR associate in the macrophages membrane and signal in conjunction to induce a regulatory phenotype. In the tumor microenvironment, apoptotic cells are abundant due to hypoxia, and PAF-like phospholipids are generated. Engagement of PAFR expressed by tumor macrophages and dendritic cells induces a regulatory/tolerogenic phenotype and subverts the innate and adaptive immune response to the tumor. During cancer therapies, PAFR-ligands can be generated, further aggravating the immune suppression. Moreover, some tumor cells express PAFR and its activation by PAFR-ligands generated during chemotherapy induce anti-apoptotic factors, which protect the tumor cells from death induced by these treatments. It is proposed that PAFR antagonists, administered in combination with chemotherapy, may represent a promising strategy for cancer treatment.

• Authors: Sonia Jancar, Roger Chammas
• Journal: Current drug targets (Curr Drug Targets) Vol. 15 Issue 10 Pg. 982-7 ( 2014) ISSN: 1873-5592 [Electronic] United Arab Emirates
• PMID: 25182608 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Platelet Membrane Glycoproteins
• Receptors, G-Protein-Coupled
• platelet activating factor receptor

Topics

• Adaptive Immunity
• Humans
• Immunity, Innate
• Macrophages (metabolism)
• Neoplasms (drug therapy, immunology, metabolism, pathology)
• Platelet Membrane Glycoproteins (antagonists & inhibitors, metabolism)
• Receptors, G-Protein-Coupled (antagonists & inhibitors, metabolism)
• Tumor Microenvironment