δ-catenin在星形细胞瘤中过表达并促进其增殖与侵袭能力  

Overexpression of δ-catenin in Astrocytoma Enhanced Tumor Proliferation and Invasiveness

作　　者：王明昊[1] 仇波[1] 王勇[1] 王军[1] 班允超[1] 崔晓[1] 景治涛[1] 王运杰[1] 

机构地区：[1]中国医科大学附属第一医院神经外科,辽宁沈阳110001

出　　处：《中国神经肿瘤杂志》2013年第2期79-85,共7页Chinese Journal of Neuro-Oncology

基　　金：国家自然科学基金青年科学基金项目(No.81000565;31100770)

摘　　要：背景与目的:δ-catenin是连环蛋白家族中的新成员,其表达与星形细胞瘤的病理分级、细胞增殖与侵袭能力的关系尚不清楚。本研究通过检测δ-catenin在星形细胞瘤中的表达和模式与病理分级的关系,并应用胶质瘤细胞系探讨δ-catenin对其生物学行为的影响。方法:应用免疫组织化学方法对156例Ⅰ~Ⅳ级星形细胞瘤进行了δ-catenin表达检测,并分别采用转染和siRNA干扰的方法调控U251和U87胶质瘤细胞系中δ-catenin的表达,通过Western blotting、MTT、Transwell和克隆形成实验等对δ-catenin的功能进行研究。结果:δ-catenin表达于正常脑组织的神经元中,但正常胶质细胞和Ⅰ级毛细胞型星形细胞瘤中无表达(0%,0/11);在Ⅱ级星形细胞瘤中的表达阳性率仅为18%(11/61),明显低于Ⅲ~Ⅳ级的35%(29/84),差异显著(P<0.01)。转染δ-catenin可明显上调Rac1的活性,促进U251细胞的增殖和克隆形成数量,明显增强细胞的侵袭能力,使用Rac1抑制剂则明显抑制U251细胞的侵袭力;使用siRNA沉默U87细胞中δ-catenin的表达后则显著降低细胞侵袭力。结论:δ-catenin的表达与星形细胞瘤的组织学分级正相关。δ-catenin可能通过上调Rac1的活性促进胶质瘤细胞的增殖与侵袭。δ-catenin可作为星形细胞瘤生物学行为的标志物,并有望成为治疗该肿瘤的新靶点。BACKGROUND ＆ OBJECTIVE： As a new member of catenin family, δ-catenin expression has been found in a few malignancies. However, its expression pattern and contribution to astrocytoma histopathology, cell proliferation and invasion are still unclear. In current study, the expression level and pattern of δ-catenin and their relationship with histopathological grade were investigated. Furthermore, several glioma cell lines were employed to explore the effects of δ-catenin on their biological features. METHODS： δ-catenin expression in 156 human astrocytoma samples （WHO grade I -IV） and its function in astroeytoma cell lines were studied using immunohistoehemistry, siRNA knockdown, transfection, MTT, transwell migration, clone formation assay and Racl pulldown techniques. RESULTS： Positive expression of -catenin protein was detected in neurons of normal brain tissue but negative in grade I astrocytoma （0%, 0/11） and glial cells from normal brain tissue using immunohistochemistry. δ-catenin expression was significantly higher in grade III-IV （35%, 29/84） compared to grade II astrocytoma cells （18%, 11/61）, and the difference was statistically significant （P 〈 0.01）. Additionally, δ-catenin overexpression promoted proliferation, invasiveness and Racl activity of U251 astrocytoma cells. Treatment of ^-catenin-transfected U251 cells with a Racl inhibitor decreased Racl activity and cell invasiveness. δ-catenin knockdown in U87 cells decreased cell proliferation, invasiveness and Racl activity. CONCLUSIONS： The results suggest that δ-catenin expression is positively correlated to the histopathological grade and associated with the malignant progression of astrocytoma. δ-catenin perhaps promotes astrocytoma cell invasion through up-regulation of Racl activity. δ-catenin may serve as a useful marker of the biological behaviors and a new therapeutic target of astrocytoma.

关 键 词：胶质瘤 星形细胞瘤 δ-catenin 表达 增殖 侵袭 

分 类 号：R739.41[医药卫生—肿瘤]