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Delta-like ligand 4 (DII4) is a protein with a negative regulatory effect on angiogenesis.[1][2] This means that this ligand will actually causes angiogenesis to stop in tissues where it is found. 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 DII4 on tumor vascularity and growth.[3] 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 DII4 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. [4]


copied from Angiogenesis

  1. ^ Lobov IB, Renard RA, Papadopoulos N, Gale NW, Thurston G, Yancopoulos GD, Wiegand SJ (February 2007). "Delta-like ligand 4 (Dll4) is induced by VEGF as a negative regulator of angiogenic sprouting". Proceedings of the National Academy of Sciences of the United States of America. 104 (9): 3219–24. Bibcode:2007PNAS..104.3219L. doi:10.1073/pnas.0611206104. PMC 1805530. PMID 17296940.
  2. ^ 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 (February 2007). "Dll4 signalling through Notch1 regulates formation of tip cells during angiogenesis". Nature. 445 (7129): 776–80. Bibcode:2007Natur.445..776H. doi:10.1038/nature05571. PMID 17259973.
  3. ^ Segarra M, Williams CK, Sierra ML, Bernarndo M, McCormick PJ, Meric D, Regino C, Choyke P, Tosato G. 2008. Dll4 activation of Notch signaling reduces tumore vascularity and inhibits tumor growth. Blood Journal. 112(5): 1904-1911
  4. ^ Dongheon Lee, Dongin Kim, Yu Bin Choi, Kyungjae Kang, Eun-Sil Sung, Jin-Hyung Ahn, Junseo Goo, Dong-Hoon Yeom, Hyun Sook Jang, Kyung Duk Moon, Sang Hoon Lee, Weon-Kyoo You MAbs. 2016 Jul; 8(5): 892–904. Published online 2016 Apr 6. doi: 10.1080/19420862.2016.1171432

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