Sprouting angiogenesis Sprouting angiogenesis. The change in balance between angiogenesis stimulators and inhibitors (angiogenic switch) and especially local upregulation of VEGF and formation of the VEGF gradient leads to stimulation of vascular responses known as sprouting angiogenesis. Stimulated blood vessels undergo a series of structural changes that consist of localized dissociation of pericytes ("dropout") from the endothelial tube, dissolution of the basement membrane and recruitment of the angiogenesis-directing cells (tip cells) from the endothelial monolayer (phalanx cells). Capillaries enlarge (to form mother vessels) and deploy cohorts of endothelial cells (stalk cells) led by VEGF gradient-seeking tip cells expressing high levels of VEGFR2 and DLL4. Interaction of tip cell-related DLL4 with NOTCH on following stalk cells suppresses VEGFR2 expression on the latter cell subset and ensures that they don't become superfluous tip cells. Vascular sprouts extend and undergo lumen formation. TIE2–expressing monocytic cells orchestrate the encounter and connection (anastomosis) of nearby sprouts to complete the formation of a functional vascular loop. Capillary loops can extend further to promote an increased tissue perfusion, a process known as looping angiogenesis, and operative during granulation tissue formation. 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: http://hemonc.mhmedical.com/DownloadImage.aspx?image=/data/Books/1791/tanbas5_Ach11_f004.png&sec=124304328&BookID=1791&ChapterSecID=124304305&imagename= Accessed: October 30, 2017 Copyright © 2017 McGraw-Hill Education. All rights reserved