LPA receptor-mediated signaling regulates cell motility and survival to anticancer drug of pancreatic cancer cells under glucose-deprived and hypoxic conditions

In tumor microenvironment, cancer cells can adapt to low conditions of nutrients and oxygen. Lysophosphatidic acid (LPA) receptor-mediated signaling is involved in the promotion of malignant properties in cancer cells. In the present study, to examine the roles of LPA receptors in the regulation of cell motility and survival to cisplatin (CDDP) of pancreatic cancer PANC-1 cells under glucose-deprived and hypoxic conditions, cells were cultured in 4500 mg/L high glucose (HG)-DMEM, 500 mg/L middle glucose (MG)-DMEM and 100 mg/L low glucose (LG)-DMEM at 21% and 1% O₂. The expression levels of LPAR1 and LPAR2 genes in cells cultured in MG-DMEM and LG-DMEM were significantly elevated, compared with HG-DMEM cells. The cell motility and survival rate to CDDP of cells cultured in MG-DMEM and LG-DMEM were significantly lower than those of cells cultured in HG-DMEM. The cell survival to CDDP was enhanced by LPA₁ knockdown and suppressed by LPA₂ knockdown. Under hypoxic conditions (1% O₂), LPAR1, LPAR2 and LPAR3 expressions were markedly higher in cells cultured in MG-DMEM and LG-DMEM than in cells cultured in HG-DMEM. The cell survival rates to CDDP of cells cultured in MG-DMEM and LG-DMEM were elevated in comparison with HG-DMEM. The cell survival to CDDP was reduced by LPA₃ knockdown. These results suggest that LPA receptor-mediated signaling is involved in the regulation of malignant properties of PANC-1 cells under glucose-deprived and hypoxic conditions.