1. Angiogenic switch and progression during tumor development
Angiogenic switch and progression during tumor development. Preangiogenic state in early tumor development is marked by the preponderance of angiogenesis inhibitors (TSP-1, PEDF, PEX), which override the effects of angiogenic stimulators (VEGF) expressed at low levels. Aggressive tumor growth is triggered by the change in balance between these factors, leading to the increase in the net stimulatory activity and the onset of angiogenesis ("angiogenic switch"). The underlying qualitative and quantitative changes in levels of angiogenesis stimulators and inhibitors are driven by tumor microenvironment (hypoxia, inflammation) and genetic progression of cancer cells (mutations in oncogenes and tumor suppressors). Continued escalation of these molecular changes with progressive disease may result in exuberant proangiogenic microenvironment with increasingly active and redundant stimulatory networks (angiogenesis progression), but excessive amounts of VEGF may be incompatible with robust angiogenesis. Abbreviations: PEDF, pigment epithelium derived factor (angiogenesis inhibitor); TSP-1, thrombospondin 1; PEX, non-catalytic fragment of MMP (all angiogenesis inhibitors); FGF, fibroblast growth factor; IL-8, interleukin 8; VEGF, vascular endothelial growth factor/VEGF-A (angiogenesis stimulators); see text.
Source: Angiogenesis, The Basic Science of Oncology, 5e
Citation: Tannock IF, Hill RP, Bristow RG, Harrington L. The Basic Science of Oncology, 5e; 2016 Available at: Accessed: October 16, 2017
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