Molecular Basis for the Regulation of Angiogenesis by Thrombospondin-1 and -2
Top Cited Papers
- 31 January 2012
- journal article
- review article
- Published by Cold Spring Harbor Laboratory in Cold Spring Harbor Perspectives in Medicine
- Vol. 2 (5), a006627
- https://doi.org/10.1101/cshperspect.a006627
Abstract
Thrombospondins TSP-1 and TSP-2 are potent endogenous inhibitors of angiogenesis. They inhibit angiogenesis through direct effects on endothelial cell migration, proliferation, survival, and apoptosis and by antagonizing the activity of VEGF. Several of the membrane receptor systems and signal transduction molecules that mediate the effects of TSP-1 and TSP-2 have been elucidated. TSP-1 and TSP-2 exert their direct effects through CD36, CD47, and integrins. Recent data indicate that CD36 and β1 integrins collaborate to transmit the signals that are initiated by TSP-1 and TSP-2. Furthermore, these receptors appear to associate with VEGFR2 to form a platform for the integration of positive and negative signals for angiogenesis. Cross talk between pro- and antiangiogenic signal transduction pathways may enable TSP-1 and TSP-2 to inhibit angiogenesis by antagonizing survival pathways while also activating apoptotic pathways. CD36 and CD47 are both involved in the suppression of nitric oxide (NO). Advances in understanding of the molecular regulation of angiogenesis by TSP have paved the way for innovations in experimental treatment of cancers and will likely continue to offer vast avenues for discovery in other disease processes as well.Keywords
This publication has 95 references indexed in Scilit:
- Human stem cells expressing novel TSP-1 variant have anti-angiogenic effect on brain tumorsOncogene, 2010
- Life history of eNOS: Partners and pathwaysCardiovascular Research, 2007
- Enhanced proangiogenic signaling in thrombospondin-1-deficient retinal endothelial cellsMicrovascular Research, 2006
- Endothelial nitric oxide synthase is critical for ischemic remodeling, mural cell recruitment, and blood flow reserveProceedings of the National Academy of Sciences of the United States of America, 2005
- The antiangiogenic effect of thrombospondin-2 is mediated by CD36 and modulated by histidine-rich glycoproteinMatrix Biology, 2005
- Role of Nitric Oxide in the Modulation of AngiogenesisCurrent Pharmaceutical Design, 2003
- The cell biology of thrombospondin-1Matrix Biology, 2000
- Binding and displacement of vascular endothelial growth factor (VEGF) by thrombospondin: Effect on human microvascular endothelial cell proliferation and angiogenesisAngiogenesis, 1999
- CD36 Mediates the In Vitro Inhibitory Effects of Thrombospondin-1 on Endothelial CellsThe Journal of cell biology, 1997
- Specific inhibition of endothelial cell proliferation by thrombospondinBiochemical and Biophysical Research Communications, 1990