LPA5-mediated signaling induced by endothelial cells and anticancer drug regulates cellular functions of osteosarcoma cells

Abstract

Lysophosphatidic acid (LPA) signaling via LPA receptors (LPA₁ to LPA₆) regulates a variety of malignant properties of cancer cells. It is known that endothelial cells promote tumor progression and chemoresistance. The present study aimed to investigate the roles of LPA₅ in cellular functions modulated by endothelial cells and anticancer drug in osteosarcoma cells. Human osteosarcoma MG-63 cells were maintained in endothelial F2 cell supernatants. After culturing for 3 months, MG63-F2 cells were established. LPAR5 expression level in MG63-F2 cells was significantly elevated, compared with MG-63 cells. The cell motile activity of MG63-F2 cells was markedly higher than that of MG-63 cells. To validate the effects of LPA₅ on cell motile activity, LPA₅ knockdown cells were generated from MG-63 cells. The cell motile activity of MG-63 cells was inhibited by LPA₅ knockdown. The cell survival to cisplatin (CDDP) was reduced in MG-63 cells treated with LPA. In the presence of LPA, the cell survival rate was significantly lower in MG63-F2 cells than MG-63 cells, correlating with LPAR5 expression. LPA₅ knockdown cells indicated the high cell survival rate to CDDP. Moreover, LPAR5 expression level was increased in the long-term CDDP treated MG63-C cells. The cell survival to CDDP of MG63-C cells was enhanced by LPA₅ knockdown. These results suggest that cellular functions are regulated through LPA₅-mediatd signaling induced by endothelial cells and CDDP in MG-63 cells.

Keywords: Cisplatin; Endothelial cells; LPA(5); Lysophosphatidic acid; Osteosarcoma cells.