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Apoptotic Cells Initiate Endothelial Cell Sprouting via Electrostatic Signaling

Department of Cancer Biology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas

Requests for reprints: Isaiah J. Fidler, Department of Cancer Biology, The University of Texas M.D. Anderson Cancer Center, Unit 173, P.O. Box 301429, Houston, TX 77230-1429. Phone: 713-792-8577; Fax: 713-792-8747; E-mail: ifidler{at}mdanderson.org.

Angiogenesis, the development of new blood vessels from preexisting vessels, is crucial to tissue growth, repair, and maintenance. This process begins with the formation of endothelial cell sprouts followed by the proliferation and migration of neighboring endothelial cells along the preformed extensions. The initiating event and mechanism of sprouting is not known. We show that the phenotypic expression of negatively charged membrane surface in apoptotic cells initiates the formation of directional endothelial cell sprouts that extend toward the dying cells by a mechanism that involves endothelial cell membrane hyperpolarization and cytoskeleton reorganization but is independent of diffusible molecules. (Cancer Res 2005; 65(24): 11529-35)

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