Section of Pharmacology, Department of Molecular Biology, University of Siena, Siena, Italy.
Eur Cytokine Netw. 2009 Dec;20(4):164-70. doi: 10.1684/ecn.2009.0169.
As tumors grow, their original vasculature can be insufficient to supply the growing tissue mass, and consequently local hypoxia develops. Thus neovascularisation is a key feature determining growth and metastasis of malignant tumors. This is, at least in part, mediated by humoral factors known to stimulate angiogenesis, such as vascular endothelial growth factor (VEGF) and fibroblast growth factor-2 (FGF-2). Among the multiple angiogenic modulators released by tumor and stromal cells, a key role is played by nitric oxide (NO). Beside its capacity to regulate permeability and blood flow, NO has been reported to exert angiogenic properties in various tumor models. The focus of this review will be the proangiogenic role of NO in the tumor microenvironment and its multiple mechanism of action on vascular endothelium. Particular attention will be devoted to the role of NO in regulating metalloproteinase activity on cultured microvascular endothelium and in the in vivo rabbit cornea assay. Finally, the potential clinical outcomes and expectations related to this topic will be discussed.
随着肿瘤的生长，其原有的血管系统可能不足以供应不断生长的组织团块，因此会出现局部缺氧。因此，新血管生成是决定恶性肿瘤生长和转移的关键特征。这至少部分是由已知能刺激血管生成的体液因子介导的，如血管内皮生长因子（VEGF）和成纤维细胞生长因子-2（FGF-2）。在肿瘤和基质细胞释放的多种血管生成调节剂中，一氧化氮（NO）起着关键作用。除了调节通透性和血流的能力外，NO 还被报道在各种肿瘤模型中具有血管生成特性。本综述的重点将是 NO 在肿瘤微环境中的促血管生成作用及其对血管内皮的多种作用机制。特别关注的是 NO 在调节培养的微血管内皮细胞中金属蛋白酶活性以及在体内兔角膜试验中的作用。最后，将讨论与该主题相关的潜在临床结果和预期。
