Tip cell: whose side are you on? Endothelial tip cells and non-tip cells in angiogenesis

The specialized endothelial tip cells which lead growing vascular sprouts in angiogenesis may be an attractive target for anti-angiogenesis therapy in cancer and eye disease. These cells initiate the angiogenic process, regulate sprout behavior, and differ in their gene expression from other endothelial cell (EC) phenotypes, such as the proliferating stalk cells that follow tip cells. Although several growth factors and signaling molecules have been identified to play a role in tip cell and stalk cell differentiation, anti-tip cell therapy still remains to be developed. In fact, a lack of appropriate models that allow discrimination between tip cells from non-tip cells has slowed down the development of selective anti-tip cell therapies. In this thesis, the CD34⁺ tip cell model was used to identify tip cells and to purify tip cell and non-tip cell populations in vitro to study the cellular and molecular regulation as well as the metabolism of tip cells and non-tip cells. Finally, the potential of different EC phenotypes as targets for anti-angiogenesis therapies in cancer was critically evaluated.