Angiogenesis and its role in the behavior of astrocytic brain tumors

Abstract

Angiogenesis, the development of new vessels from a pre-existing vasculature, accompanies the growth and malignant transformation of astrocytic brain tumors. Neovascularization is essential for sustained tumor growth, and with increasing grade, astrocytic tumors undergo an, angiogenic switch, manifested by marked increases in vessel density and changes in vascular morphology. In the quiescent state, endogenous anti-angiogenic factors including endostatin, thrombospondin, and soluble vascular endothelial growth factor receptor-1 (sVEGFR-1) balance the actions of pro-angiogenic stimuli and restrain the angiogenic switch. Once activated, pro-angiogenic factors including most notably basic fibroblast growth factor (FGF), vascular endothelial growth factor (VEGF-A), and platelet-derived growth factor (PDGF) incite robust astrocytoma neovascularization. Recent studies have also explored the expression patterns and functional importance of the angiopoietins, Tie2 and neuropilin receptors, and hepatocyte growth factor/scatter factor (HGF). Together these angiogenic factors have diverse actions on endothelium and perivascular supporting cells that engender tumor neovessels with a unique phenotype, distinct from normal vessels. Properties of the astrocytoma neovasculature contribute to tumor growth, malignant progression, invasion, hemorrhage, and edema formation. Thus, the mechanistic actions of angiogenic factors on cerebral microvessels and the nature of the resultant tumor neovasculature establish a framework for understanding many of the characteristic behaviors of astrocytoma tumors.