lysophosphatidylserine and Brain-Neoplasms

Lysophosphatidylserine (LPS) was found to stimulate intracellular calcium increase in U87 human glioma cells. LPS also stimulated chemotactic migration of U87 human glioma cells, which was completely inhibited by pertussis toxin (PTX). Moreover, LPS was also found to stimulate ERK, p38 MAPK, JNK, and Akt activities in U87 cells. We observed that LPS-induced U87 chemotaxis was mediated by PI3K, p38 MAPK, and JNK. LPS-induced chemotactic migration in U87 cells was inhibited by Ki16425, an LPA(1/3) receptor-selective antagonist, which suggested that the Ki16425-sensitive G-protein coupled receptor (GPCR) played a role in this process. Moreover, U87 cells were found to uniquely express LPA(1) but not LPA(2-5). In addition, LPS failed to stimulate the NF-kappaB-driven luciferase activity in exogenously LPA(1)-transfected HepG2 cells. Taken together, we propose that LPS stimulates GPCR, which is in contrast to the well-known LPA receptors, thus resulting in the chemotactic migration in U87 human glioma cells.

Topics: Brain Neoplasms; Cell Line, Tumor; Chemotaxis; Glioma; Humans; Isoxazoles; JNK Mitogen-Activated Protein Kinases; Lysophospholipids; p38 Mitogen-Activated Protein Kinases; Phosphatidylinositol 3-Kinases; Propionates; Proto-Oncogene Proteins c-akt; Receptors, G-Protein-Coupled; Receptors, Lysophosphatidic Acid