Effect of lysophosphatidylglycerol on several signaling molecules in OVCAR-3 human ovarian cancer cells: Involvement of pertussis toxin-sensitive G-protein coupled receptor

In this study, we observed that lysophosphatidylglycerol (LPG) stimulated intracellular calcium ([Ca²⁺]_i) increase in OVCAR-3 human ovarian cancer cells. LPG-stimulated [Ca²⁺]_i increase was inhibited by U-73122 but not by U-73343, suggesting that LPG stimulates calcium signaling via phospholipase C activation. Moreover, pertussis toxin (PTX) almost completely inhibited [Ca²⁺]_i increase by LPG, indicating the activation of PTX-sensitive G-proteins. LPG-induced [Ca²⁺]_i increase was only observed in OVCAR-3 ovarian cancer cells and SK-OV3 ovarian cancer cells among tested several cell types. LPG also induced extracellular signal-regulated kinase (ERK) and Akt phosphorylation in OVCAR-3 ovarian cancer cells. Pertussis toxin did not affect the LPG-induced activation of ERK and Akt phosphorylation. We also found that LPG failed to stimulate NF-κB-driven luciferase activity in exogenously LPA₁, LPA₂, or LPA₃-transfected HepG2 cells. Taken together we suggest that LPG stimulates a membrane bound receptor which is different from well-known LPA receptors (LPA₁, LPA₂, and LPA₃), resulting in at least two different signaling cascades; one involves a pertussis toxin-sensitive and phospholipase C-dependent [Ca²⁺]_i increase, and the other involves a pertussis toxin-insensitive activation of ERK and Akt in ovarian cancer cells.