Open Access

REVIEW

Molecular regulation of tumour angiogenesis by nitric oxide

Marina Ziche, Lucia Morbidelli

Section of Pharmacology, Department of Molecular Biology, University of Siena, Siena, Italy

* Corresponding Author: L. Morbidelli,

European Cytokine Network 2009, 20(4), 164-170. https://doi.org/10.1684/ecn.2009.0169

Accepted 12 June 2009;

Abstract

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 angio-genesis, 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 microenvi-ronment 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.

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Keywords

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