Editing Angiogenesis (section)

====Dll4====
[[DLL4|Delta-like ligand 4]] (Dll4) is a protein with a negative regulatory effect on angiogenesis.<ref>{{cite journal | vauthors = Lobov IB, Renard RA, Papadopoulos N, Gale NW, Thurston G, Yancopoulos GD, Wiegand SJ | title = Delta-like ligand 4 (Dll4) is induced by VEGF as a negative regulator of angiogenic sprouting | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 104 | issue = 9 | pages = 3219–3224 | date = February 2007 | pmid = 17296940 | pmc = 1805530 | doi = 10.1073/pnas.0611206104 | doi-access = free | bibcode = 2007PNAS..104.3219L }}</ref><ref>{{cite journal | vauthors = Hellström M, Phng LK, Hofmann JJ, Wallgard E, Coultas L, Lindblom P, Alva J, Nilsson AK, Karlsson L, Gaiano N, Yoon K, Rossant J, Iruela-Arispe ML, Kalén M, Gerhardt H, Betsholtz C | display-authors = 6 | title = Dll4 signalling through Notch1 regulates formation of tip cells during angiogenesis | journal = Nature | volume = 445 | issue = 7129 | pages = 776–780 | date = February 2007 | pmid = 17259973 | doi = 10.1038/nature05571 | s2cid = 4407198 | bibcode = 2007Natur.445..776H }}</ref> Dll4 is a transmembrane ligand, for the [[notch family of receptors]]. There have been many studies conducted that have served to determine consequences of the Delta-like Ligand 4. One study in particular evaluated the effects of Dll4 on tumor vascularity and growth.<ref name="pmid18577711">{{cite journal | vauthors = Segarra M, Williams CK, Sierra Mde L, Bernardo M, McCormick PJ, Maric D, Regino C, Choyke P, Tosato G | display-authors = 6 | title = Dll4 activation of Notch signaling reduces tumor vascularity and inhibits tumor growth | journal = Blood | volume = 112 | issue = 5 | pages = 1904–11 | date = September 2008 | pmid = 18577711 | pmc = 2518892 | doi = 10.1182/blood-2007-11-126045 }}</ref> In order for a tumor to grow and develop, it must have the proper vasculature. The VEGF pathway is vital to the development of vasculature that in turn, helps the tumors to grow. The combined blockade of VEGF and Dll4 results in the inhibition of tumor progression and angiogenesis throughout the tumor. This is due to the hindrance of signaling in endothelial cell signaling which cuts off the proliferation and sprouting of these endothelial cells. With this inhibition, the cells do not uncontrollably grow, therefore, the cancer is stopped at this point. if the blockade, however, were to be lifted, the cells would begin their proliferation once again.<ref>{{cite journal | vauthors = Lee D, Kim D, Choi YB, Kang K, Sung ES, Ahn JH, Goo J, Yeom DH, Jang HS, Moon KD, Lee SH, You WK | display-authors = 6 | title = Simultaneous blockade of VEGF and Dll4 by HD105, a bispecific antibody, inhibits tumor progression and angiogenesis | journal = mAbs | volume = 8 | issue = 5 | pages = 892–904 | date = July 2016 | pmid = 27049350 | pmc = 4968104 | doi = 10.1080/19420862.2016.1171432 | doi-access = free }}</ref>