Promotion of cell-invasive activity through the induction of LPA receptor-1 in pancreatic cancer cells |
| |
Authors: | Kaori Fukushima Shiho Otagaki Kaede Takahashi Kanako Minami Kaichi Ishimoto Nobuyuki Fukushima |
| |
Affiliation: | 1. Division of Molecular Oncology, Department of Life Science, Faculty of Science and Engineering, Kindai University, Higashiosaka, Osaka, Japan;2. Division of Molecular Neurobiology, Department of Life Science, Faculty of Science and Engineering, Kindai University, Higashiosaka, Osaka, Japan |
| |
Abstract: | AbstractLysophosphatidic acid (LPA) is a simple biological lipid and mediates several biological functions with LPA receptors (LPA1 to LPA6). In the present study, to assess whether LPA receptors promote cell-invasive activity of pancreatic cancer cells, highly invasion PANC-R9 cells were established from PANC-1 cells, using Matrigel-coated Cell Culture Insert. The cell-invasive activity of PANC-R9 cells was shown to be approximately 15 times higher than that of PANC-1 cells. LPAR1 expression level was markedly elevated in PANC-R9 cells in comparison with PANC-1 cells, while LPAR3 expression level was reduced. The cell-invasive activity of PANC-R9 cells was enhanced by LPA, but LPA had no impact on PANC-1 cell invasion. Before initiation of the cell invasion assay, PANC-R9 cells were pretreated with dioctanoylglycerol pyrophosphate (DGPP), an antagonist of LPA1/LPA3. The invasive activity of PANC-R9 cells was markedly suppressed by DGPP. Autotaxin (ATX) is a key enzyme that catalyzes the conversion of lysophosphatidylcholine (LPC) to LPA. ATX expression level was elevated in PANC-R9 cells compared with PANC-1 cells. In the presence of LPC, the cell motile activity of PANC-R9 cells was markedly stimulated. In contrast, LPC did not affect the cell motile activity of PANC-1 cells. PANC-R9 cell motility was inhibited by an ATX inhibitor, PF-8380. These results suggest that LPA signaling via LPA1 is a potent molecular target for the regulation of tumor progression in PANC-1 cells. |
| |
Keywords: | LPA LPA receptor-1 cell invasion pancreatic cancer cells |
|
|