Reversal of Cellular Roles in Angiogenesis: Implications for Anti-Angiogenic Therapy

Whether occurring during embryonic development, in pathophysiological conditions, such as healing/tissue regeneration, or in fully pathological conditions, such as cancer and diseases, angiogenesis is traditionally thought to be a strongly endotheliumdriven . In fact, the main features of the angiogenic model, largely preserved as first by Folkman [1] in 1971, implicate endothelial cells as primary effectors of the process [2]. As depicted in figure 1a, pro-angiogenic growth factors (especially ) trigger endothelial cell activation, proliferation and motility. In addition to resident cells, circulating endothelial precursors may also participate in the formation of neotubules [3]. Another crucial role is played by local pericytes or bone -derived pericyte progenitors [4-6]. According to the angiogenesis dogma, pericytes recruited by migrating endothelial cells to confer stability to nascent vascular structures [2,4-7]. Indeed, targeting pericytes through NG2 proteoglycan [8] or PDGFRβ [5,6] strongly neovasculogenesis and may also affect lymphangiogenesis.