Delta4, an endothelial specific notch ligand expressed at sites of physiological and tumor angiogenesis.
Delta-Notch signalling regulates cell-fate choices in a variety of tissues during development. We report the expression of Delta4 (D14) in arterial endothelium during mouse embryogenesis and in the endothelium of tumor blood vessels. The expression of D14 in the mouse begins at 8 dpc in the dorsal aortae, umbilical artery and the heart. Subsequent expression is restricted to smaller vessels and capillaries and is reduced in most adult tissues. However, it is high in the vasculature of xenograft human tumors in the mouse, in endogenous human tumors and is regulated by hypoxia. These data implicate D14 and the Notch signalling pathway in angiogenesis and suggest possible new targets for antiangiogenic tumor therapy.
Mailhos
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Developmental Genetics, Imperial Cancer Research Fund, London, England. c.mailhos@icrf.icnet.uk
Modlich
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Lewis
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Harris
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Bicknell
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Ish-Horowicz
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D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001158:Arteries / Q000502:physiology; D001798:Blood Proteins / Q000502:physiology*; D002135:Calcium-Binding Proteins; D004330:Drosophila; D029721:Drosophila Proteins; D004730:Endothelium, Vascular / Q000502:physiology*; D005260:Female; D006133:Growth Substances / Q000502:physiology*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D009389:Neovascularization, Pathologic / Q000503:physiopathology*; D018919:Neovascularization, Physiologic / Q000502:physiology*; D009928:Organ Specificity; D051880:Receptors, Notch; D015398:Signal Transduction / Q000502:physiology; D014407:Tumor Cells, Cultured
D048868:Adaptor Proteins, Signal Transducing; D001798:Blood Proteins; D002135:Calcium-Binding Proteins; C424126:DLL4 protein, human; D029721:Drosophila Proteins; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C497759:N protein, Drosophila; D051880:Receptors, Notch