Human Hepatocellular Carcinoma Tumor-derived Endothelial Cells Manifest Increased Angiogenesis Capability and Drug Resistance Compared with Normal Endothelial Cells
Human Hepatocellular Carcinoma Tumor-derived Endothelial Cells Manifest Increased Angiogenesis Capability and Drug Resistance Compared with Normal Endothelial Cells
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与正常内皮细胞相比，人肝细胞癌肿瘤来源的内皮细胞表现出增强的血管生成能力和耐药性
DOI：
10.1158/1078-0432.ccr-08-2780
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发表时间：
2009-08-01
影响因子：
11.5
通讯作者：
Tang, Zhao-You
中科院分区：
文献类型：
--
作者：
Xiong, Yu-Quan;Sun, Hui-Chuan;Tang, Zhao-You
目的：越来越多的证据表明，肿瘤来源的内皮细胞(TEC)与邻近正常组织的内皮细胞(NEC)相比，具有独特的表型，并可能对药物产生耐药性。本研究的目的是研究人肝细胞癌(HCC)来源的TECs和NECs的血管生成活性及其对药物治疗的反应。实验设计：用抗CD105抗体偶联磁珠从肝癌或邻近正常肝组织分离TECs或NECs。通过检测CD105、CD31、CD144、血管内皮生长因子受体-1、血管内皮生长因子受体-2和von Willebrand因子的表达，以及对Dil-ac-LDL摄取和管状形成能力的检测来表征内皮细胞的表型和功能特性。比较CD105(+)TECs与CD105(+)NECs和人脐静脉内皮细胞(HUVEC)的增殖能力、运动能力、对肿瘤细胞的黏附能力、对肿瘤条件培养液的反应以及对化疗药物阿霉素、5-氟尿嘧啶和抗血管生成药物索拉非尼的反应。结果：CD105(+)TECs与CD105(+)NECs和HUVEC相比，具有更强的抗凋亡、运动和促血管生成能力。同时，CD105(+)TECs具有更强的黏附肿瘤细胞和在肿瘤环境中存活的能力。CD105(+)TECs对阿霉素、5-氟尿嘧啶和索拉非尼的耐受性明显高于CD105(+)NECs和HUVEC。结论：TECs具有较强的血管生成活性，对化疗药物和血管生成抑制剂的耐受性增强，为研究肿瘤血管生成和抗血管生成药物提供了一种较好的工具。
Purpose: Increasing evidence indicates that tumor-derived endothelial cells (TEC) possess a distinct and unique phenotype compared with endothelial cells (NEC) from adjacent normal tissue and may be able to acquire resistance to drugs. The aim of this study was to investigate the angiogenesis activity and response to drug treatment of TECs and NECs derived from human hepatocellular carcinoma (HCC).Experimental Design: TECs or NECs were isolated from HCC or adjacent normal liver tissue using anti-CD105 antibody coupled to magnetic beads. The phenotypic and functional properties of endothelial cells were characterized by testing the expression of CD105, CD31, CD144, vascular endothelial growth factor receptor-1, vascular endothelial growth factor receptor-2, and von Willebrand factor, and the ability of Dil-Ac-LDL-uptake and tube formations. CD105(+) TECs were compared with CD105(+) NECs and human umbilical vein endothelial cells (HUVEC) by examining their ability to proliferate, motility, ability to adhere to tumor cells, response to tumor conditioned medium, and reactions to the chemotherapy drugs Adriamycin and 5-fluorouracil and the antiangiogenic drug sorafenib.Results: Compared with CD105(+) NECs and HUVECs, CD105(+) TECs showed increased apoptosis resistance and motility and proangiogenic properties. Meanwhile, CD105(+) TECs had a greater ability to adhere to tumor cells and survive in the tumor environment. Moreover, CD105(+) TECs acquired more resistance to Adriamycin, 5-fluorouracil, and sorafenib than CD105(+) NECs and HUVECs.Conclusions: TECs possessed enhanced angiogenic activity and resistance to chemotherapeutic drugs and an angiogenesis inhibitor, and may provide a better tool for studying tumor angiogenesis and antiangiogenesis drugs in HCC.