Transfer of Dll4 was also shown in vivo from tumor cells to host endothelium. These exosomes can transfer the Dll4 protein to other endothelial cells and incorporate it into their cell membrane, which results in an inhibition of Notch signaling and a loss of Notch receptor. It can also be incorporated into the exosomes of tumor cells that overexpress Dll4. Here, we present evidence that Dll4 is incorporated into endothelial exosomes. It is expressed in endothelial cells and regulates the differentiation between tip cells and stalk cells of neovasculature. Delta-like 4 (Dll4) is a Notch ligand that is up-regulated during angiogenesis. It is involved in a variety of developmental processes and has an essential role in vascular development and angiogenesis. Notch signaling is an evolutionary conserved pathway that is mediated by cell-cell contact.
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