Prostaglandin E2 promotes migration and adhesion in hepatocellular carcinoma cells
Prostaglandin E2 promotes migration and adhesion in hepatocellular carcinoma cells
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DOI：
10.1093/carcin/bgi022
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发表时间：
2005-04-01
期刊：
影响因子：
4.7
通讯作者：
Martín-Sanz, P
中科院分区：
文献类型：
--
作者：
Mayoral, R;Fernández-Martínez, A;Martín-Sanz, P
研究了环氧合酶-2 (COX-2) 的表达和前列腺素 E-2 (PGE(2)) 合成对细胞迁移、基质金属蛋白酶 (MMP) 分泌和人肝癌细胞系粘附的影响。基础条件下COX-2的表达与MMP-2和MMP-9的分泌之间观察到密切相关。 HuH-7 细胞中表达高组成水平的 COX-2，COX-2 的选择性抑制剂可显着抑制细胞迁移，而外源添加 PGE(2) 可增强细胞迁移。肝细胞癌 (HCC) 细胞表达 β1 和 αVβ3 整合素，表现出细胞对纤连蛋白和玻连蛋白的粘附增加。此外，PGE(2) 的添加增加了HuH-7 细胞中β1 整合素的水平和对玻连蛋白的粘附。 MEK/ERK、p38 MAPK、蛋白激酶A 和C 抑制剂会损害PGE(2) 诱导的HuH-7 细胞的迁移，表明该过程涉及多种途径。综上所述，这些结果支持 COX-2 衍生的 PGE(2) 合成与 HCC 细胞中通过整合素依赖性途径的迁移和粘附之间存在关系。
The effect of the expression of cyclooxygenase-2 (COX-2) and prostaglandin E-2 (PGE(2)) synthesis on cell migration, the secretion of matrix metalloproteinases (MMPs) and the adhesion of human hepatoma cell lines has been investigated. A close correlation was observed between the expression of COX-2 under basal conditions and the secretion of MMP-2 and MMP-9. Cell migration in HuH-7 cells, which express high constitutive levels of COX-2 was significantly inhibited by selective inhibitors of COX-2 and enhanced by exogenous addition of PGE(2). Hepatocellular carcinoma (HCC) cells expressed beta 1 and alpha V beta 3 integrins, exhibiting an increase in cell adhesion onto fibronectin and vitronectin. Moreover, addition of PGE(2) increased the beta 1 integrin levels and adhesion on vitronectin in HuH-7 cells. Inhibitors of MEK/ERK, p38 MAPK, protein kinases A and C impaired the migration of HuH-7 cells induced by PGE(2), indicating the involvement of multiple pathways in the process. Taken together, these results support the existence of a relationship between COX-2-derived PGE(2) synthesis, and migration and adhesion through an integrin-dependent pathway in HCC cells.