Roles of endothelial cells in the regulation of cell motility via lysophosphatidic acid receptor-2 (LPA2) and LPA3 in osteosarcoma cells
Roles of endothelial cells in the regulation of cell motility via lysophosphatidic acid receptor-2 (LPA2) and LPA3 in osteosarcoma cells
复制标题
骨肉瘤细胞中内皮细胞通过溶血磷脂酸受体-2（LPA2）和LPA3调节细胞运动的作用
DOI：
10.1016/j.yexmp.2020.104596
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发表时间：
2021-02-01
影响因子：
3.6
通讯作者：
Tsujiuchi, Toshifumi
中科院分区：
文献类型：
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作者：
Minami, Kanako;Ueda, Nanami;Tsujiuchi, Toshifumi
溶血磷脂酸（LPA）通过LPA受体（LPA（1）至LPA（6））的信号传导表现出多种生物学应答。在肿瘤微转移中，内皮细胞促进癌细胞功能。在本研究中，我们研究了内皮细胞在通过LPA（2）和LPA（3）调节人骨肉瘤MG-63细胞运动活性中的作用。在细胞运动实验中，内皮F2细胞培养上清可明显增强MG-63细胞的运动活性。GRI-977143（LPA（2）激动剂）可增强MG-63细胞的运动性，（2S）-OMPT（LPA（3）激动剂）可降低MG-63细胞的运动性。在通过与F2细胞上清液共培养从MG-63细胞产生的高度迁移的MG-63-CR 7（F2）细胞中，LPAR 2和LPAR 3表达增加。通过LPA处理刺激MG 63-CR 7（F2）细胞运动性。在存在F2细胞上清液的情况下，GRI-977143显著增强MG 63-CR 7（F2）细胞运动性，并且（2S）-OMPT抑制该细胞运动性。自分泌运动因子（ATX）将溶血磷脂酰胆碱（LPC）酶促转化为LPA。ATX在MG-63-CR（F2）细胞中的表达高于MG-63细胞。与MG-63细胞相比，LPC显著增加MG-63-CR 7（F2）细胞的运动性。此外，LPC处理的F2细胞的上清液显著刺激MG 63-CR（F2）细胞运动。提示内皮细胞通过LPA（2）和LPA（3）激活LPA信号通路参与MG-63细胞运动活性的调节。
Lysophosphatidic acid (LPA) signaling via LPA receptors (LPA(1) to LPA(6)) exhibits a variety of biological responses. In tumor micmenvironment, endothelial cells promote cancer cell functions. In this study, we investigated the roles of endothelial cells in the regulation of cell motile activity via LPA(2) and LPA(3) in human osteosarcoma MG-63 cells. In cell motility assay, the cell motile activity of MG-63 cells was markedly increased by the supernatants of endothelial F2 cells. MG-63 cell motility elevated by the supernatants was enhanced by GRI-977143 (LPA(2) agonist) and reduced by (2S)-OMPT (LPA(3) agonist). LPAR2 and LPAR3 expressions were increased in highly migratory MG63-CR7(F2) cells, which were generated from MG-63 cells by co-culture with F2 cell supernatants. MG63-CR7(F2) cell motility was stimulated by LPA treatment. In the presence of F2 cell supernatants, MG63-CR7(F2) cell motility was markedly enhanced by GRI-977143 and suppressed by (2S)-OMPT. Autotaxin (ATX) enzymatically converts lysophosphatidylcholine (LPC) to LPA. ATX expression was higher in MG63-CR(F2) cells than in MG-63 cells. MG63-CR7(F2) cell motility was markedly increased by LPC in comparison with MG-63 cells. In addition, MG63-CR(F2) cell motility was significantly stimulated by the supernatants of LPC treated F2 cells. The present results suggest that the activation of LPA signaling via LPA(2) and LPA(3) by endothelial cells is involved in the modulation of cell motile activity of MG-63 cells.