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

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.