The N-Terminal Domain of Thrombospondin-1: a Key for the Dual Effect of TSP-1 in Angiogenesis and Cancer Progression?

Verônica Morandi

doi:10.1100/tsw.2009.11

Abstract

The data presented in this article suggest that intact TSP-1 may act, in normal vessel homeostasis, as an angiostatic factor favoring vessel quiescence, or even vessel regression, but this activity would be largely impaired in the presence of an excess of angiogenic stimuli and proteases. The fact that the N-terminal domain of TSP-1 (heparin-binding domain or HBD) is recognized by a plethora of cell receptors, all of them engaged in proangiogenic responses, strongly suggests that the proteolytic cleavage of HBD may be relevant in certain pathophysiological conditions.

Highlights

Universidade do Estado do Rio de Janeiro (UERJ), Departamento de Biologia Celular, Laboratório de Biologia da Célula Endotelial e da Angiogênese, Rua São Francisco Xavier, 524 – PHLC sala 205, Maracanã – Rio de Janeiro – RJ, Brazil
Thrombospondin-1 (TSP-1), the most studied of a family of five extracellular glycoproteins[1], which is expressed by cells in tissues, was first identified as a major constituent of platelet α-granules[2]
The high expression of TSP-1 in patients with colorectal liver metastasis leads to poor prognosis[20], suggesting that the protective role conferred by inhibition of angiogenesis is overcome when cancer cells spread beyond their primary niche

Summary

Introduction

Universidade do Estado do Rio de Janeiro (UERJ), Departamento de Biologia Celular, Laboratório de Biologia da Célula Endotelial e da Angiogênese, Rua São Francisco Xavier, 524 – PHLC sala 205, Maracanã – Rio de Janeiro – RJ, Brazil. TSRs act through the CD36 receptor on microvascular endothelial cells by inducing their apoptosis[6,7]. Experimental overexpression of TSP-1 in many in vivo models and the naturally occurring high expression of TSP-1 in many cancer patients have been associated with a significant increase in survival rates[8].

Results

Conclusion