Endothelin-1 and angiogenesis in cancer

Tumours require oxygenation, nutrition and a route for dissemination. This necessitates the development of new vessels or angiogenesis. High levels of new vessel development are indicators of poor prognosis in cancer; they also provide new avenues of anti-tumour therapy. Angiogenesis in cancer produces structurally different vessels from angiogenesis in wound healing and inflammation. This article reviews the differences between vessels in tumour angiogenesis and normal angiogenesis. The main focus of the article is the role of the vasoactive peptide endothelin-1 (ET-1) in tumour angiogenesis. The role of ET-1 in tumour development is reviewed, before the direct and indirect effects of ET-1 in angiogenesis are examined. ET-1 has a direct angiogenic effect on endothelial and peri-vascular cells. It also has an indirect action through the increased release of the potent pro-angiogenic substance vascular endothelial growth factor (VEGF), via hypoxia inducible factor-1. ET-1 also indirectly stimulates angiogenesis by stimulating fibroblasts and cancer cells to produce pro-angiogenic proteases. ET-1 is a novel stimulator of tumour angiogenesis and warrants further examination as an anti-angiogenic treatment target.