摘要
目的 探讨HAb18G/CD14 7诱导肝癌细胞基质金属蛋白酶 (MMP)分泌和活化的机制。方法 应用明胶酶谱分析方法观察HAb18G/CD14 7分子及其细胞内、外片段高表达对人SMMC 772 1肝癌细胞分泌MMP(MMP 2和MMP 9)及其活化的影响 ,以及细胞内Ca2 +信号调控在此过程的作用。结果 HAb18G/CD14 7分子的高表达明显诱导MMP 2和MMP 9的分泌和活化 ,分泌总量升高 ( 30 .4 5± 3.4 1) % (P <0 .0 1) ,而细胞内、外各片段的表达均不能有效刺激MMP的分泌与活化。细胞内Ca2 +库释放诱导剂Thapsigargin(Tg)在未转染 772 1细胞可有效诱导MMP 2和MMP 9的分泌与活化 ,较对照组升高 ( 5 8.6 3± 31.0 4 ) % (P <0 .0 5 ) ,其诱导作用可受到细胞内Ca2 +调节抑制剂S 亚硝基 乙酰青霉胺 (S nitroso N acetylpenicillamine,SNAP)的明显抑制 ,而HAb18G/CD14 7的高表达则抑制了以上细胞内Ca2 +信号通路对MMP分泌和活化的调节作用 ,使转染的T772 1细胞MMP的分泌与活化始终处于高水平稳定状态。结论 全长的HAb18G/CD14 7分子可通过抑制细胞内Ca2 +信号调控通路诱导肝癌细胞稳定高表达和活化MMP。
Objective To investigate the mechanisms of secretion and activation of matrix metalloproteinases (MMPs) induced by high expression of HAb18G/CD147 in human hepatoma cells. Methods Gelatin zymography analysis was carried out by using human 7721 hepatoma cells line, HAb18G/CD147-expressed T7721 cells and its intracellular or extracellular fragments-expressed cells (T7721δN and T7721δC) as cell models. Thapsigargin (Tg), an inducer of intracellular Ca 2+ store depletion, and S -nitroso- N -acetylpenicillamine (SNAP), an inhibitor of intracellular Ca 2+ mobilization, were introduced into above cell culture systems to investigate the involvement of Ca 2+ signal regulation in processes of HAb18G-induced MMP secretion and activation. Results Expression of HAb18G/CD147 enhanced secretion and activation of MMPs (MMP-2 and MMP-9) in human hepatoma was increased to (30.45±3.41)% in compare with non-transfected SMMC-7721 cells, P < 0.01 . But truncation of HAb18G/CD147 attenuated the effect of HAb18G/CD147 on secretion of MMPs. Tg enhanced release and activation of MMPs (MMP-2 and MMP-9) in non-transfected SMMC-7721 cells, compared to the control with (58.63±31.04)% ( P < 0.05 ), and this effect was negatively regulated by SNAP. No any effect of Tg and SNAP were observed in T7721 cells expressed HAb18 G/CD147 ( P > 0.05 ). Conclusion Full length of HAb18G/CD147 is necessary for inducing secretion and activation of MMPs in human hepatoma cells via inhibited intracellular Ca 2+ mobilization.
出处
《肿瘤》
CAS
CSCD
北大核心
2004年第6期534-537,共4页
Tumor
基金
国家 8 63计划重点课题 (编号:2 0 0 1AA2 15 10 1)
国家自然科学基金资助项目(编号 :3 0 2 0 0 14 4)
