Induction of lysophosphatidic acid receptor-3 by 12-O-tetradecanoylphorbol-13-acetate stimulates cell migration of rat liver cells.

12-O-tetradecanoylphorbol-13-acetate (TPA) which is one of tumor promoting agents stimulates cell migration ability of several tumor cells. In the present study, we investigated whether lysophosphatidic acid (LPA) receptors are involved in cell migration of rat liver cells stimulated by TPA. The rat liver epithelial WB-F344 and hepatoma RH7777 cells were treated by TPA for 48h. The expression levels of LPA receptor genes in those cells were measured by real-time reverse transcription (RT)-polymerase chain reaction (PCR) analysis. The expressions of the LPA receptor-3 (Lpar3) gene were significantly elevated in WB-F344 and RH7777 cells treated by TPA, but not Lpar1 and Lpar2 genes. In cell migration assay, TPA treatment showed markedly high cell migration in both cells. The pretreatment with inhibitors of Gi protein suppressed those migration abilities. We next generated the Lpar3 knockdown cells from WB-F344 cells and investigated the effect on cell migration. Interestingly, the cell migration of the knockdown cells was not stimulated by TPA. These results suggest that TPA-stimulated cell migration of rat liver cells may be mainly dependent on the LPA(3)-mediated effect.