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Tumor endothelial markers (TEMs) are significantly up-regulated during angiogenesis and neoangiogensis that are crucial for the growth of solid tumors. TEMs localized on the cell surface and conserved across species are of particular interest for future development of anti-angiogenic therapies. These include TEMs such as TEM1, TEM5, TEM7 and TEM8. TEM5 is a member of the adhesion family of G protein coupled receptors and is localized on the surface of endothelial cells. TEM5 is a seven-pass transmembrane receptor, unlike TEM1, TEM7 and TEM8 which span the membrane once. TEM5 is abundantly expressed in tumor vessels, heart, placenta, ovary, small intestine, and colon. Proteolytically processed soluble TEM5 mediates endothelial cell survival during angiogenesis by linking integrin to glycosaminoglycans.