Lysophosphatidic Acid Receptors Determine Tumorigenicity and Aggressiveness of Ovarian Cancer Cells

Abstract

Lysophosphatidic acid (LPA, 1-acyl-2-lyso-sn -glycero-3-phosphate), the simplest glycerophospholipid, mediates a wide range of biologic actions, including stimulation of DNA synthesis, cell proliferation, cytoskeleton reorganization, cell survival, drug resistance, cell adhesion, migration, cytokine production, and ion transport ( 1 , 2 ). The biologic functions of extracellular LPA are mediated through specific G protein -coupled receptors (GPCRs), including Edg-2/ LPA1, Edg-4/LPA2, and Edg-7/LPA3, that belong to the endothelial differentiation gene (Edg) family ( 3 -5 ). Other members of the Edg family, Edg-1/S1P1, Edg-3/S1P3, Edg-5/S1P2, Edg-6/S1P4, and Edg-8/S1P5, are high-affinity receptors for the structurally related lysophospholipid sphingosine 1-phosphate (S1P) ( 6 , 7 ). LPA receptors may heterodimerize, thereby increasing their selectivity and broadening their spectrum of activity ( 8 ). Recently, the GPCRs GPR23/p2y9 (LPA4) ( 9 ), GPR92/93 (LPA5) ( 10 , 11 ), GPR87/95 (LPA6) ( 12 ), p2y5 ( 13 ), and p2y10 (