Enhancement of endothelial cell migration by constitutively active LPA1-expressing tumor cells

Highlights: ► Mutated LPA1 stimulates cell migration of endothelial cells. ► VEGF expressions are increased by mutated LPA1. ► LPA signaling via mutated LPA1 is involved in angiogenesis. ► Mutated LPA1 promotes cancer cell progression. -- Abstract: Lysophosphatidic acid (LPA) receptors belong to G protein-coupled transmembrane receptors (LPA receptors; LPA1 to LPA6). They indicate a variety of cellular response by the interaction with LPA, including cell proliferation, migration and differentiation. Recently, we have reported that constitutive active mutated LPA1 induced the strong biological effects of rat neuroblastoma B103 cells. In the present study, we examined the effects of mutated LPA1 on the interaction between B103 cells and endothelial F-2 cells. Each LPA receptor expressing B103 cells were maintained in serum-free DMEM and cell motility assay was performed with a Cell Culture Insert. When F-2 cells were cultured with conditioned medium from Lpar1 and Lpar3-expressing cells, the cell motility of F-2 cells was significantly higher than control cells. Interestingly, the motile activity of F-2 cells was strongly induced by mutated LPA1 than other cells, correlating with the expression levels of vascular endothelial growth factor (Vegf)-A and Vegf-C. Pretreatment of LPA signaling inhibitors inhibited F-2 cell motility stimulated by mutated LPA1. These results suggest that activation of LPA signaling via mutated LPA1 may play an important role in the promotion of angiogenesis in rat neuroblastoma cells.