Dll4-containing exosomes induce capillary sprout retraction in a 3D microenvironment
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Sharghi-Namini-2014-DII4-containing exosomes.pdf
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Author(s)
Sharghi-Namini, Soheila
Tan, Evan
Ong, Lee Ling
Ge, Ruowen
Asada, Haruhiko
Date Issued
February 2014
Journal
Scientific Reports
Publisher
Nature Publishing Group
Citation
Sharghi-Namini, Soheila, Evan Tan, Lee-Ling Sharon Ong, Ruowen Ge, and H. Harry Asada. “Dll4-Containing Exosomes Induce Capillary Sprout Retraction in a 3D Microenvironment.” Sci. Rep. 4 (February 7, 2014).
Version
Final published version
Abstract
Delta-like 4 (Dll4), a membrane-bound Notch ligand, plays a fundamental role in vascular development and angiogenesis. Dll4 is highly expressed in capillary endothelial tip cells and is involved in suppressing neighboring stalk cells to become tip cells during angiogenesis. Dll4-Notch signaling is mediated either by direct cell-cell contact or by Dll4-containing exosomes from a distance. However, whether Dll4-containing exosomes influence tip cells of existing capillaries is unknown. Using a 3D microfluidic device and time-lapse confocal microscopy, we show here for the first time that Dll4-containing exosomes causes tip cells to lose their filopodia and trigger capillary sprout retraction in collagen matrix. We demonstrate that Dll4 exosomes can freely travel through 3D collagen matrix and transfer Dll4 protein to distant tip cells. Upon reaching endothelial sprout, it causes filopodia and tip cell retraction. Continuous application of Dll4 exosomes from a distance lead to significant reduction of sprout formation. This effect correlates with Notch signaling activation upon Dll4-containing exosome interaction with recipient endothelial cells. Furthermore, we show that Dll4-containing exosomes increase endothelial cell motility while suppressing their proliferation. These data revealed novel functions of Dll4 in angiogenesis through exosomes.
MIT Department
Massachusetts Institute of Technology. Department of Mechanical Engineering
d'Arbeloff Lab for Information Sytems and Technology (Massachusetts Institute of Technology)
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Creative Commons Attribution-Noncommercial
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DOI of Published Version
https://doi.org/10.1038/srep04031
