Kato Kohei, Yoshikawa Kyohei, Tanabe Eriko, Kitayoshi Misaho, Fukui Rie, Fukushima Nobuyuki, Tsujiuchi Toshifumi
Division of Cancer Biology and Bioinformatics, Department of Life Science, Faculty of Science and Engineering, Kinki University, 3-4-1, Kowakae, Higashiosaka, Osaka, 577-8502, Japan.
Tumour Biol. 2012 Oct;33(5):1739-44. doi: 10.1007/s13277-012-0433-0. Epub 2012 Jun 8.
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 (LPA(1)) and LPA(3) 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 LPA(1) and LPA(3) 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 LPA(1) and LPA(3) play the different roles on cell migration ability of pancreatic cancer cells, suggesting the opposite effects via LPA(1) and LPA(3) may contribute to the pathogenesis of pancreatic cancers in hamsters.
溶血磷脂酸（LPA）与至少六种G蛋白偶联跨膜LPA受体相互作用。最近，已经证明每个LPA受体作为细胞功能的正向或负向调节因子。在本研究中，为了评估LPA受体对胰腺癌细胞迁移的生物学作用，我们通过用短发夹RNA质粒转染从仓鼠胰腺癌细胞中生成了LPA受体-1（LPA(1)）和LPA(3)敲低细胞，并测量了它们的细胞运动和侵袭能力。在细胞运动和侵袭试验中，使用涂有或未涂有基质胶的细胞培养插入物。虽然Lpar1敲低细胞的细胞运动和侵袭比对照细胞明显增强，但Lpar3敲低细胞显示出明显较低的细胞运动和侵袭。此外，为了研究LPA(1)和LPA(3)在胰腺癌发生中的作用，我们还测量了由亚硝基化合物诱导的仓鼠胰腺导管腺癌（PDA）中Lpar1和Lpar3基因的表达水平。PDA中Lpar1基因的表达明显低于正常胰腺组织。相比之下，在PDA中检测到Lpar3基因的表达升高。因此，我们证明LPA(1)和LPA(3)在胰腺癌细胞的细胞迁移能力上发挥不同作用，提示通过LPA(1)和LPA(3)的相反作用可能有助于仓鼠胰腺癌的发病机制。
