Dong Yan, Hirane Miku, Araki Mutsumi, Fukushima Nobuyuki, Honoki Kanya, Tsujiuchi Toshifumi
Division of Cancer Biology and Bioinformatics, Department of Life Science, Faculty of Science and Engineering, Kinki University, 3-4-1, Kowakae, Higashiōsaka, Osaka, 577-8502, Japan.
Mol Cell Biochem. 2014 Aug;393(1-2):17-22. doi: 10.1007/s11010-014-2042-2. Epub 2014 Mar 28.
LPA signaling via LPA receptors [LPA receptor-1 (LPA1)-LPA6] mediates the several cellular responses in cancer cells, including cell motility and invasion. In the present study, to investigate a role of LPA5 in the cell motile and invasive activities of sarcoma cells, LPAR5 knockdown (HOSL5 and HT1080L5) cells were generated from human osteosarcoma HOS and fibrosarcoma HT1080 cells, respectively. In cell motility assays with cell culture inserts, HOSL5 and HT1080L5 cells indicated the high cell motile activities, compared with control cells. The cell invasive activities of HOSL5 and HT1080L5 cells were significantly higher than those of control cells. Moreover, the activities of matrix metalloproteinase (MMP)-2 and MMP-9 were measured by gelatin zymography. MMP-2 was significantly activated in HOSL5 cells, but not MMP-9. The elevated activities of MMP-2 and MMP-9 were found in HT1080L5 cells, in comparison with control cells. These results suggest that LPA signaling via LPA5 negatively regulates the cell motile and invasive activities of human sarcoma cells.
溶血磷脂酸（LPA）通过LPA受体[LPA受体-1（LPA1）-LPA6]介导癌细胞中的多种细胞反应，包括细胞迁移和侵袭。在本研究中，为了探究LPA5在肉瘤细胞的细胞迁移和侵袭活性中的作用，分别从人骨肉瘤HOS细胞和纤维肉瘤HT1080细胞中生成了LPAR5敲低（HOSL5和HT1080L5）细胞。在使用细胞培养插入物的细胞迁移试验中，与对照细胞相比，HOSL5和HT1080L5细胞表现出较高的细胞迁移活性。HOSL5和HT1080L5细胞的细胞侵袭活性显著高于对照细胞。此外，通过明胶酶谱法测定基质金属蛋白酶（MMP）-2和MMP-9的活性。MMP-2在HOSL5细胞中被显著激活，但MMP-9未被激活。与对照细胞相比，HT1080L5细胞中发现MMP-2和MMP-9的活性升高。这些结果表明，通过LPA5的LPA信号传导负调节人肉瘤细胞的细胞迁移和侵袭活性。
