Blockade of Dll4 inhibits tumour growth by promoting non-productive angiogenesis

摘要: Tumour growth requires accompanying expansion of the host vasculature, with tumour progression often correlated vascular density. Vascular endothelial factor (VEGF) is best-characterized inducer angiogenesis. We report that VEGF dynamically regulates expression Delta-like ligand 4 (Dll4), which was previously shown to be absolutely required for normal embryonic development. To define Dll4 function in angiogenesis, we manipulated this pathway murine models using several approaches. Here show blockade resulted markedly increased vascularity, associated enhanced angiogenic sprouting and branching. Paradoxically, vascularity non-productive—as by poor perfusion hypoxia, most importantly, decreased growth—even tumours resistant anti-VEGF therapy. Thus, VEGF-induced acts as a negative regulator angiogenesis; its results striking uncoupling from vessel density, presenting novel therapeutic approach even therapies. VEGF, or factor, has become an important tool cancer But not effective against all tumours, so search alternative approaches continues. Two groups week one such could Dll4, 4. This transmembrane molecule part Notch signalling pathway. It known essential development blood vessels embryo: new work shows it also may viable — potentially well tolerated patients solid are One two papers showing inhibition Dll4-mediated inhibits deregulation