Thrombospondin-based antiangiogenic therapy.
Thrombospondins (TSPs) are a family of extracellular matrix proteins that regulate tissue genesis and remodeling. TSP-1 plays a pivotal role in the regulation of both physiological and pathological angiogenesis. The inhibitory effects of TSP-1 on angiogenesis have been established in numerous experimental models. Among other TSP members, TSP-2 has equivalent domain structure as TSP-1 and shares most functions of TSP-1. The mechanisms by which TSP-1 and -2 inhibit angiogenesis can be broadly characterized as direct effects on vascular endothelial cells and indirect effects on the various angiogenic regulators. The fact that TSP-1 and -2 are potent endogenous angiogenic inhibitors has prompted studies to explore their therapeutic applications, and detailed understanding of the mechanisms of action of TSP-1 and -2 has facilitated the design of therapeutic strategies to optimize these activities. The therapeutic effects can be achieved by up-regulation of endogenous TSPs, or by the delivery of recombinant proteins or synthetic peptides that contain sequences from the angiogenic domain of TSP-1. In this article, we review the progress in thrombospondin-based antiangiogenic therapy and discuss the perspectives on the significant challenges that remain.
Zhang
Xuefeng
X
Department of Surgery, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA.
Lawler
Jack
J
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D042783:Endothelial Cells / Q000187:drug effects*; D004730:Endothelium, Vascular / Q000166:cytology; D006801:Humans; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000378:metabolism; D019699:Thrombospondins / Q000145:classification / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use*
D020533:Angiogenesis Inhibitors; D019699:Thrombospondins