整合素β3胞浆段尾部序列对αvβ3介导的细胞行为的影响  

Differential roles of amino acid sequences of integrin β3 cytoplasmic tail in αvβ3-mediated cell behaviors

作　　者：周玉兰[1] 黄建松[1] 刘萍[1] 施小凤[1] 崔雄鹰[1] 阮铮[1] 奚晓东[1] 

机构地区：[1]上海交通大学医学院附属瑞金医院上海血液学研究所医学基因组学国家重点实验室,上海200025

出　　处：《内科理论与实践》2012年第5期378-383,共6页Journal of Internal Medicine Concepts & Practice

基　　金：国家自然科学基金(项目编号:81070414)

摘　　要：目的:探讨在与整合素αv复合的模式下,整合素β3亚基胞浆段序列在肿瘤细胞的黏附、伸展和迁移中所起的作用,从而为寻找干扰肿瘤进展的分子靶点提供思路。方法:利用中国仓鼠卵巢(CHO)细胞模型,建立共表达整合素αv与整合素β3全长及其T758、Y759位截短体的稳定细胞株,检测各稳定细胞株在固相化的αvβ3配体玻璃黏连蛋白上的黏附、伸展功能,运用transwell观察各细胞株的迁移能力。结果:稳定表达整合素αvβ3全长的CHO细胞具有在固相化玻璃黏连蛋白上的黏附、伸展和迁移能力。相较于CHO-αvβ3全长细胞株,CHO-αvβ3△758截短体细胞株的黏附、伸展以及迁移能力均明显受损;而CHO-αvβ3△759截短体细胞株仍保留着黏附能力,但伸展能力减弱,并且迁移能力受损明显。结论:整合素β3胞浆尾端YRGT和RGT氨基酸序列在αvβ3介导的细胞黏附和迁移方面发挥不同的作用,提示β3亚基胞内段参与调控肿瘤细胞的重要细胞行为,是潜在的肿瘤治疗靶点。Objective To study the effect of integrin β3 subunit cytoplasmic domain on adhesion, spreading and migration of tumor cells, and providing insights into the molecular targets for interfering the progress of tumor. Methods Stable Chinese hamster ovary （CHO） cell lines that co-express human integrin αv and full length β3 or mutant β3 with truncation at COOH terminal T75s or yTs9 were established. Spreading and adhesion of CHO-αvβ3, CHO-αvβ3/k758 and CHO-αvβ3 A759 cells on immobilized vitronectin were examined and transwell assay was performed to evaluate the migration ability of the cell lines. Results The CHO cells transfected with integrin αv and wild-type integrin β3（CHO- αvβ3 cells） had the ability of attachment, spreading and migration on immobilized vitronectin. Compared with CHO-αvβ3 cells, CHO cells transfected with integrin αv and integrin β3 truncated at 3,758 （CHO-αvβ3 A758 cells） failed to attach, spread or migrate on immobilized vitroncctin, while CHO cells tranfected with integrin αv and integrin β3 truncated at y^799 （CHO-αvβ3 A759 cells） were able to attach on immobilized vitronectin but with an impaired ability of spreading and migration. Conclusions The integrin β3 subunit cytoplasmic domain plays an important role in adhesion, spreading and migration of αvβ3-expressing cells, and in which the RGT and YRGT sequences of integrin β3 cytoplasmic tail act differentially. Data suggest that these sequences may represent the therapeutic targets for treatment of tumor.

关 键 词：整合素ΑVΒ3 截短体 黏附 迁移 

分 类 号：R730.2[医药卫生—肿瘤]