摘要
目的 研究层粘连蛋白受体α6 β1整合素在人肝癌细胞侵袭行为中的作用。 方法 采用dominantnegative策略 ,以无功能的α6 β4 TR代替细胞表面α6 β1受体 ,从而消除了人肝癌细胞Bel740 2α6 β1受体的功能。用划痕法和Boyden小室法分别检测细胞的迁移和侵袭 ,明胶酶谱分析法检测细胞基质金属蛋白酶 (matrixmetalloproteinases,MMPs)的分泌。结果 消除α6 β1功能的人肝癌细胞迁移能力明显降低 ;侵袭并穿透人工基膜的细胞数降低 46 .7% ;MMP 9的分泌几乎被完全抑制 ,活化型的MMP 2降低 43.9%。结论 人肝癌细胞在层粘连蛋白基质上的迁移、侵袭及MMPs的分泌和活化主要由α6 β1受体介导。肝癌组织中层粘连蛋白和整合素α6 β1的高表达 。
Objective To study the mechanism of enhanced invasiveness of human hepatocellular carcinoma (HCC) by laminin (LN) receptor integrin α6β1.Methods A stable transfectant of HCC Bel 7402 cell line, the α6β1 receptors of which were replaced by non functional LN receptor α6β4 TR using dominant negative strategy, was used. Motility of the non transfected, mock transfected and transfected tumor cells was assessed by the number of cells migrated to an area scratched out of cells on tumor cell monolayer. Tumor cell invasion was examined by cell penetration through a Matrigel layer in Boyden chamber. Matrix metalloproteinases (MMPs) secretion was detected by gelatin zymography.Results The migration of HCC Bel 7402 cells expressing dominant negative α6β1 was significantly decreased. Their invasive capability was decreased by 46.7%. The secretion of MMP 9 was almost totally inhibited and the activated MMP 2 was decreased by 43.9%.Conclusion The decrease in cell motility, invasiveness and MMPs secretion of HCC cells expressing dominant negative α6β4 TR implies that LN integrin interaction plays important role in HCC progression.
出处
《中华肿瘤杂志》
CAS
CSCD
北大核心
2000年第4期287-289,共3页
Chinese Journal of Oncology
基金
国家自然科学基金资助项目 !(39780 0 38)
关键词
肝肿瘤
肿瘤侵袭
肿瘤转移
层粘连蛋白
整合素
Liver neoplasms
Carcinoma, hepatocellular
Neoplastic invasion
Neoplastic metastasis
Laminin
Integrin
