Opposite roles of LPA1 and LPA3 on cell motile and invasive activities of pancreatic cancer cells
- 203 Downloads
Lysophosphatidic acid (LPA) interacts with at least six G protein-coupled transmembrane LPA receptors. Recently, it has been demonstrated that each LPA receptor acts as a positive or negative regulator of cellular function. In the present study, to assess a biological role of LPA receptors on cell migration of pancreatic cancer cells, we generated LPA receptor-1 (LPA1) and LPA3 knockdown cells from hamster pancreatic cancer cells by transfection with short hairpin RNA plasmids and measured their cell motile and invasive abilities. In cell motility and invasion assay, a Cell Culture Insert, coated with or without a Matrigel, was used. While the cell motility and invasion of Lpar1 knockdown cells were markedly enhanced than those of control cells, Lpar3 knockdown cells showed significantly lower cell motility and invasion. Moreover, to investigate an involvement of LPA1 and LPA3 in the development of pancreatic cancers, we also measured the expression levels of Lpar1 and Lpar3 genes in hamster pancreatic duct adenocarcinomas (PDAs) induced by a nitroso compound. The expressions of Lpar1 gene in PDAs were significantly lower than those in normal pancreatic tissues. By contrast, the elevated expressions of Lpar3 gene were detected in PDAs. We thus demonstrate that LPA1 and LPA3 play the different roles on cell migration ability of pancreatic cancer cells, suggesting the opposite effects via LPA1 and LPA3 may contribute to the pathogenesis of pancreatic cancers in hamsters.
KeywordsLPA LPA receptor Cell migration Invasion Pancreatic cancer
This study was supported in part by a grant-in-aid (20591765) for Scientific Research from Ministry of Education, Culture, Sports, Science and Technology of Japan, and by grants (21321201) from the Ministry of Health, Labor and Welfare of Japan, and by grants (RK-027) from the Faculty of Science and Engineering, Kinki University.
Conflicts of interest
- 10.Edwards BK, Brown MI, Wingo PA, Howe H, Ward E, Ries LA, Schrag D, Jamison PM, Jemal A, Wu XC, Friedman C, Harlan L, Warren J, Anderson RN, Pickle LW. Annual report to the nation on the status of cancer, 1975-2002, featuring population-based trends in cancer treatment. J Natl Cancer Inst. 2005;97:1407–27.CrossRefPubMedGoogle Scholar
- 11.Tsujiuchi T, Furukawa M, Yamasaki A, Hotta M, Kusunoki C, Suyama N, Mori T, Honoki K, Fukushima N. Infrequent mutation of lysophosphatidic acid receptor-1 gene in hamster pancreatic duct adenocarcinomas and established cell lines. J Toxicol Pathol. 2009;22:89–92.CrossRefPubMedPubMedCentralGoogle Scholar
- 21.Shida D, Kitayama J, Yamaguchi H, Hama K, Aoki J, Arai H, Yamashita H, Mori K, Sako A, Konishi T, Watanabe T, Sakai T, Suzuki R, Ohta H, Takuwa Y, Nagawa H. Dual mode regulation of migration by lysophosphatidic acid in human gastric cancer cells. Exp Cell Res. 2004;301:168–78.CrossRefPubMedGoogle Scholar
- 24.Okabe K, Hayashi M, Kato K, Okumura M, Fukui R, Honoki K, Fukushima N, Tsujiuchi T. Lysophosphatidic acid receptor-3 increases tumorigenicity and aggressiveness of rat hepatoma RH7777 cells. Mol Carcinog. 2012. doi: 10.1002/mc.21851.