整合素介导低剪切力诱导的肝癌细胞迁移

Integrins Mediate the Migration of HepG2 Cells Induced by Low Shear Stress

低剪切力是肿瘤体内微环境的组成部分,是调控肿瘤细胞迁移、侵袭的重要因素。作为细胞膜表面受体,整合素(integrin)不仅介导细胞与细胞外基质之间的黏附,而且作为细胞的重要力学感受器起到整合细胞内的力学、化学信号的作用。本研究的目的是探讨低剪切力引起肝癌细胞整合素的变化及其对肝癌细胞迁移的影响。采用低剪切力(1.4dyn/cm2)作用于肝癌HepG2细胞,划痕法测定在0、1、2、4h细胞的迁移情况,F-actin染色观察低剪切力作用2h和4h后细胞骨架的变化,Western blot测定integrinα亚基在瞬时(15s和30s)、短时(5、15和30min)和长时(1、2和4h)的表达规律。结果表明:与对照组比较,低剪切力刺激HepG2细胞后,细胞迁移距离显著增加,应力纤维丝排列规则,integrinα亚基在不同的时间点的表达呈现出时序性的差异,提示integrin的不同亚基在剪切力诱导肝癌细胞迁移中具有不同的调控作用。

Low shear stress is a component of the tumor microenvironment in vivo and plays a key role in regulating cancer cell migration and invasion. The integrin, as a mechano-sensors mediating and integrating mechanical and chemical signals, induce the adhesion between cells and extracellular matrix （ECM）. The purpose of this study is to investigate the effect of low shear stress（1.4 dyn/cmz）on the migration of HepG2 cells and the expression of inte- grin. Scratch wound migration assay was performed to examine the effect of low shear stress on the migration of HepG2 cells at 0 h, 1 h, 2 h and 4 h, respectively. F-actin staining was used to detect the expression of F-actin in HepG2 ceils treated with low shear stress at 2 h and 4 h. Western blot analysis was carried out to determine the effect of low shear stress on the expression of integrin at different durations. The results showed that the migrated distance of HepG2 cells and the expression of F-actin increased significantly compared with the controls. The integrin a subunits showed a different time-dependent expression, suggesting that various subunits of integrin exhibit differ- ent effects in tow shear stress regulating cancer cells migration.