Differential function of lysophosphatidic acid receptors in cell proliferation and migration of neuroblastoma cells

Lysophosphatidic acid (LPA) is a bioactive lipid mediator that induces diverse cellular biological effects and interacts with G protein-coupled transmembrane LPA receptors. In the present study, to assess biological roles of LPA receptors in the pathogenesis of tumor cells, each LPA receptor (Lpar1, Lpar2 or Lpar3)-expressing rat neuroblastoma B103 cells (lpa1-1, lpa2-2 or lpa3-3-2 cells, respectively) were used. In cell motility and invasion assay, lpa2-2 and lpa3-3-2 cells showed significant higher intrinsic activity without LPA treatment than LPA receptor-unexpressing AB2-1bf cells. LPA treatment further increased cell motility of these cells, which was suppressed by the pretreatment with inhibitors of Gi, Gq protein, or ROCK. By contrast, lpa1-1 cells markedly decreased intrinsic cell motility and invasion, compared with AB2-1bf cells. Constitutively active mutant Lpar1-expressing cells (lpa1Δ-1) showed significant high motility, comparable with those of lpa2-2 and lpa3-3-2. In soft agar assay, lpa3-3-2 and lpa1Δ-1 cells showed colony formation, but other cells failed. These results suggest that LPA receptors may play different roles in cell proliferation and migration of rat neuroblastoma cells.