Dual mode regulation of migration by lysophosphatidic acid in human gastric cancer cells
Dual mode regulation of migration by lysophosphatidic acid in human gastric cancer cells
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DOI：
10.1016/j.yexcr.2004.08.008
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发表时间：
2004-12-10
影响因子：
3.7
通讯作者：
Nagawa, H
中科院分区：
文献类型：
--
作者：
Shida, D;Kitayama, J;Nagawa, H
溶血磷脂酸（LPA）与至少三种G蛋白偶联受体（GPCR）LPA 1/Edg-2、LPA 2/Edg-4和LPA 3/Edg-7相互作用，是对各种细胞具有不同作用的脂质介质。在这里，我们研究了LPA受体的表达谱和LPA诱导的胃癌细胞迁移模式。北方印迹分析显示，各种胃癌细胞表达不同水平的LPA 1、LPA 2和LPA 3，但没有一致的模式。使用Boyden室测定，LPA显着增加表达LPA 1的细胞的细胞迁移，其效果几乎完全被Kil 6425，一种LPA拮抗剂对LPA 1和LPA 3消除。相比之下，LPA本身并不显著诱导MKN 28和MKN 74细胞的迁移，这些细胞仅表达LPA 2。然而，当肝细胞生长因子（HGF）与LPA一起放置在下室时，LPA以剂量依赖性方式诱导这些细胞迁移。免疫沉淀分析显示LPA诱导表达LPA 2的细胞中c-Met的瞬时酪氨酸磷酸化，这表明LPA对c-Met的反式激活导致与HGF协同迁移至这些细胞。我们的研究结果表明，LPA调节胃癌细胞的迁移在一个受体特异性的方式，并建议LPA受体的表达模式可能会影响胃癌的转移行为。(C)2004爱思唯尔公司All rights reserved.
Lysophosphatidic acid (LPA), which interacts with at least three G protein-coupled receptors (GPCRs), LPA I /Edg-2, LPA2/Edg-4, and LPA3/Edg-7, is a lipid mediator with diverse effects on various cells. Here, we investigated the expression profiles of LPA receptors and patterns of LPA-induced migration in gastric cancer cells. Northern blot analysis revealed that various gastric cancer cells expressed variable levels of LPA1, LPA2, and LPA3 without a consistent pattern. Using a Boyden chamber assay, LPA markedly increased cell migration of LPA1-expressing cells, the effects of which were almost totally abrogated by Kil6425, anLPA antagonist against LPA1 and LPA3. In contrast, LPA by itself did not significantly induce migration in MKN28 and MKN74 cells, which exclusively expressed LPA2. However, when hepatocyte growth factor (HGF) was placed with LPA in the lower chamber, LPA induced migration of these cells in a dose-dependent manner. Inummoprecipitation analysis revealed that LPA induced transient tyrosine phosphorylation of c-Met in LPA2-expressing cells, which suggests that the transactivation of c-Met by LPA causes a cooperative migratory response with HGF to these cells. Our results indicate that LPA regulates the migration of gastric cancer cells in a receptor-specific manner and suggest that the expression pattern of LPA receptors may affect the metastatic behavior of gastric cancer. (C) 2004 Elsevier Inc. All rights reserved.