Thrombospondin-based antiangiogenic therapy.

Journal Article (Journal Article;Review)

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.

Full Text

Duke Authors

Cited Authors

  • Zhang, X; Lawler, J

Published Date

  • September 2007

Published In

Volume / Issue

  • 74 / 2-3

Start / End Page

  • 90 - 99

PubMed ID

  • 17559888

Pubmed Central ID

  • PMC2100421

International Standard Serial Number (ISSN)

  • 0026-2862

Digital Object Identifier (DOI)

  • 10.1016/j.mvr.2007.04.007

Language

  • eng

Conference Location

  • United States