IQGAP1诱导肝细胞肝癌干性促进血管生成拟态形成的实验研究  

IQGAP1 promotes vasculogenic mimicry by increasing stemness in hepatocellular carcinoma

作　　者：陈辰 孙慧誌 刘铁菊[1] 梁晓辉[1] 赵楠[1] 董学易[1] 赵秀兰[1] Chen Chen;Huizhi Sun;Tieju Liu;Xiaohui Liang;Nan Zhao;Xueyi Dong;Xiulan Zhao(Department of Pathology, Tianjin Medical University, Tianjin 300070, Chin)

机构地区：[1]天津医科大学病理学教研室,天津市300070

出　　处：《中国肿瘤临床》2018年第7期339-344,共6页Chinese Journal of Clinical Oncology

基　　金：国家自然科学基金项目(编号:81572872)资助~~

摘　　要：目的:检测IQGAP1在肝细胞肝癌(hepatocellular carcinoma,HCC)组织中的表达并研究其对肝癌细胞血管生成拟态形成能力的影响。方法:采用免疫组织化学法检测2001年1月至2009年1月天津医科大学肿瘤医院180例肝癌组织中IQGAP1的表达,采用CD31/PAS双染法检测肝癌中血管生成拟态的情况,并分析IQGAP1与血管生成拟态之间的相关性;将IQGAP1过表达质粒和干扰质粒分别转染至肝癌细胞系Hep G2和SMMC7721中,使用Western blot法检测转染后Hep G2和SMMC7721细胞中干性相关蛋白CD133、CD44、Sox2和ALDH1的表达情况;细胞功能学实验检测IQGAP1对迁移侵袭、增殖、管道形成能力的影响。结果:免疫组织化学结果显示IQGAP1定位于细胞膜或细胞质,其表达与肿瘤分级、转移和血管生成拟态形成相关(P<0.05)。在Hep G2细胞中上调IQGAP1,增强了Hep G2细胞迁移侵袭、增殖、管道行成能力,促进了干性相关蛋白CD133、CD44、Sox2和ALDH1的表达;在SMMC7721细胞中下调IQGAP1,抑制了SMMC7721细胞迁移侵袭、增殖、管道行成能力(P<0.05),降低了上述干性相关蛋白的表达。结论:IQGAP1表达升高促进了HCC的恶性生物学行为,IQGAP1可能通过诱导HCC干性来促进血管生成拟态形成。Objective： To examine the expression of IQGAP1 in hepatocellular carcinoma and its effect on vasculogenic mimicry（VM）.Methods： Immunohistochemical staining was performed to investigate the expression of IQGAP1. CD31/PAS double staining was performed to detect VM and analyze the correlation of IQGAP1 and VM. Hep G2 cells were transfected with an IQGAP1 overexpression plasmid to induce exogenous expression of IQGAP1, and an IQGAP1 knockdown plasmid was transfected into SMMC7721 cells to reduce IQGAP1 levels. The expression of cancer stem cell markers CD133, CD44, Sox2, and ALDH1 was analyzed by Western blot and compared with that in the control. Cellular functional experiments were used to determine the role of IQGAP1 in promoting cancer cells＇ ability of invasiveness and migration, proliferation, and VM formation. Results： Immunohistochemical analysis revealed that IQGAP1 was mainly located in the cell membrane and/or cytoplasm, and the staining intensity was correlated with tumor grade, metastasis, and VM（P0.05）. Cells transfected with the overexpression plasmid showed enhanced CD133, CD44, Sox2, and ALDH1 levels due to the increase in IQGAP1 and exhibited increased invasion ability, proliferation, and VM formation. In the SMMC7721 cells transfected with the knockdown plasmid, CD133, CD44, Sox2, and ALDH1 levels were decreased and motility was inhibited. Conclusions：IQGAP1 supports malignant behavior in hepatocellular carcinoma and may promote VM by increasing stemness.

关 键 词：肝细胞肝癌 血管生成拟态 IQGAP1 转移 干性 

分 类 号：R735.7[医药卫生—肿瘤]