Dutour A, Rigaud M
Center for Cell and Gene Therapy, Baylor College of Medicine, 1102 Bates Street, Houston, TX 77030, USA.
Anticancer Res. 2005 Nov-Dec;25(6B):3799-807.
Angiogenesis is a complicated process, essential for tumor progression and metastasis. Extensive work has been done to understand the mechanisms of tumor angiogenesis and identify angiogenesis inhibitors. It is now recognised that tumor endothelial cells present different functional and phenotypic characteristics than normal resting endothelial cells. These differences and advances in molecular biology have allowed the development of selective agents targeting tumor endothelial cells as therapeutic approaches for cancer. These new targeted strategies need to be evaluated in relevant models before being transferred from the laboratory bench to the clinic. In vivo tumor models remain a good way to evaluate the effect of these agents on tumor growth and metastasis. Nevertheless, in parallel to the development of tumor angiogenesis inhibitors, in vitro models have been designed to mimic angiogenesis steps and enable the evaluation of these new drugs. In this paper, after reviewing the phenotypic characteristics of tumor endothelial cells that make them easy to target for antiangiogenic therapy, some of the most commonly used in vitro and in vivo models, which enable the evaluation of antiangiogenic agents, are presented and discussed.
血管生成是一个复杂的过程,对肿瘤进展和转移至关重要。为了解肿瘤血管生成的机制并识别血管生成抑制剂,已经开展了大量工作。现在人们认识到,肿瘤内皮细胞呈现出与正常静息内皮细胞不同的功能和表型特征。这些差异以及分子生物学的进展使得开发靶向肿瘤内皮细胞的选择性药物成为癌症的治疗方法。这些新的靶向策略在从实验室工作台转移到临床之前,需要在相关模型中进行评估。体内肿瘤模型仍然是评估这些药物对肿瘤生长和转移影响的好方法。然而,在肿瘤血管生成抑制剂发展的同时,体外模型也已被设计用于模拟血管生成步骤,并能够评估这些新药。在本文中,在回顾了使肿瘤内皮细胞易于成为抗血管生成治疗靶点的表型特征之后,介绍并讨论了一些最常用的能够评估抗血管生成药物的体外和体内模型。