Phosphatidylserine is a marker of tumor vasculature and a potential target for cancer imaging and therapy
Phosphatidylserine is a marker of tumor vasculature and a potential target for cancer imaging and therapy
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DOI：
10.1016/s0360-3016(02)03928-7
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发表时间：
2002-12-01
影响因子：
7
通讯作者：
Thorpe, PE
中科院分区：
文献类型：
--
作者：
Ran, S;Thorpe, PE
目的：（1）研究小鼠实体瘤血管内皮细胞是否存在磷脂酰丝氨酸（PS）暴露。(2)要确定PS曝光是否可以诱导活的内皮细胞在组织培养的条件下存在的肿瘤microenvironment.Methods和材料：Externalized PS在体内检测通过注射小鼠与单克隆抗PS抗体和检查冷冻切片的肿瘤和正常组织的抗PS抗体结合到血管endothelial。凋亡细胞用抗活性caspase-3抗体或TUNEL法鉴定。结果：抗PS抗体与6种肿瘤模型的血管内皮细胞特异性结合。在不同类型的肿瘤中，PS阳性血管的百分比范围为4%至40%。正常器官血管内皮素不染色。极少数肿瘤血管表达凋亡标记物。缺氧/复氧，酸度，炎性细胞因子，凝血酶，或过氧化氢诱导PS暴露在培养的内皮细胞，而不造成的损失violations.Conclusions：血管内皮细胞在肿瘤，但不是在正常组织，externalize PS。PS暴露可能是由肿瘤相关的氧化应激和激活的细胞因子引起的。PS是一种丰富的肿瘤血管标记物，可用于肿瘤的显像和治疗。(C)2002年爱思唯尔科技有限公司
Purpose: (1) To determine whether exposure of phosphatidylserine (PS) occurs on vascular endothelium in solid tumors in mice. (2) To determine whether PS exposure can be induced on viable endothelial cells in tissue culture by conditions present in the tumor microenvironment.Methods and Materials: Externalized PS in vivo was detected by injecting mice with a monoclonal anti-PS antibody and-examining frozen sections of tumors and normal tissues for anti-PS antibody bound to vascular endothelium. Apoptotic cells were identified by anti-active caspase-3 antibody or by TUNEL assay. PS exposure on cultured endothelial cells was determined by I-125-annexin V binding.Results: Anti-PS antibody bound specifically to vascular endothelimn in six tumor models. The percentage of PS-positive vessels ranged from 4% to 40% in different tumor types. Vascular endothelimn in normal organs was unstained. Very few tumor vessels expressed apoptotic markers. Hypoxia/reoxygenation, acidity, inflammatory cytokines, thrombin, or hydrogen peroxide induced PS exposure on cultured endothelial cells without causing loss of viability.Conclusions: Vascular endothelial cells in tumors, but not in normal tissues, externalize PS. PS exposure might he induced by tumor-associated oxidative stress and activating cytokines. PS is an abundant and accessible marker of tumor vasculature and could be used for tumor imaging and therapy. (C) 2002 Elsevier Science Inc.