Vascular endothelial growth factor as a marker of tumor endothelium.
Vascular endothelial growth factor as a marker of tumor endothelium.
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DOI：
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发表时间：
1998-05
期刊：
影响因子：
11.2
通讯作者：
R. Brekken;Xianming Huang;S. King;P. Thorpe
中科院分区：
文献类型：
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作者：
R. Brekken;Xianming Huang;S. King;P. Thorpe
血管内皮生长因子（VEGF）是一种血管生成生长因子，是实体瘤血管化的主要刺激物。VEGF的产生是由肿瘤细胞中的致癌基因突变和肿瘤块内的缺氧条件诱导的。缺氧和局部VEGF浓度升高导致肿瘤内皮细胞上VEGF受体表达上调。因此，在肿瘤微环境中，VEGF及其受体均有上调，导致其在肿瘤血管内皮上被占据的受体浓度较高。血管内皮生长因子受体复合物提供了一个有吸引力的目标，为特定的递送药物或其他效应器到肿瘤内皮。在目前的研究中，已经提出了几种分泌针对VEGF受体（Flk-1）复合物或VEGF本身的单克隆抗体的杂交瘤。其中三种抗体（3E7、GV39M和11B5）在ELISA中与VEGF:Flk-1复合物以及人肿瘤、啮齿动物肿瘤和人肿瘤异种移植物冷冻切片中的肿瘤内皮具有高亲和力。3E7和GV39M经人肿瘤移植小鼠静脉注射后可选择性定位于肿瘤内皮。此外，表达了一种阻断VEGF与KDR/Flk-1相互作用的抗体（2C3）。2C3在体外可抑制vegf介导的内皮细胞生长，并在人肿瘤移植小鼠体内强烈定位于肿瘤结缔组织。这些发现表明3E7、GV39M和2C3是肿瘤血管或结缔组织靶向和成像的候选分子。
Vascular endothelial growth factor (VEGF) is an angiogenic growth factor that is a primary stimulant of the vascularization of solid tumors. VEGF production is induced by oncogenic gene mutations in the tumor cells and by hypoxic conditions inside the tumor mass. Hypoxia and the locally increased concentration of VEGF lead to an up-regulation of VEGF receptor expression on tumor endothelial cells. Therefore, in the tumor microenvironment, there is an up-regulation of both VEGF and its receptor, leading to a high concentration of occupied receptor on tumor vascular endothelium. The VEGF:receptor complex presents an attractive target for the specific delivery of drugs or other effectors to tumor endothelium. In the present study, several hybridomas that secrete monoclonal antibodies against the VEGF:receptor (Flk-1) complex or against VEGF itself have been raised. Three of the antibodies (3E7, GV39M, and 11B5) bind with high affinity to the VEGF:Flk-1 complex in ELISA and to tumor endothelium in frozen sections of human tumors, rodent tumors, and human tumor xenografts. 3E7 and GV39M localize selectively to tumor endothelium after i.v. injection into mice bearing human tumor xenografts. Additionally, one antibody (2C3) was raised that blocks the interaction between VEGF and KDR/Flk-1. 2C3 inhibits VEGF-mediated growth of endothelial cells in vitro and localizes strongly to connective tissue in tumors after injection into mice bearing human tumor xenografts. These findings suggest that 3E7, GV39M, and 2C3 are candidates for targeting and imaging the vasculature or connective tissue of tumors.