Thrombospondins (TSP) are secreted proteins with the ability to inhibit angiogenesis.
The thrombospondins (TSP) are a family of multifunctional proteins. The family consists of thrombospondins 1-5 and can be divided into 2 subgroups: A, which contains TSP-1 and -2, and B, which contains TSP-3, -4 and -5 (also designated cartilage oligomeric protein or COMP). TSP-1 and -2 are homotrimers, consisting of three identical subunits, whereas TSP-3, -4 and -5 are homopentamers.
TSP-1 was first isolated from platelets that had been stimulated with thrombin, and so was designated 'thrombin-sensitive protein'. Since its first recognition, functions for TSP-1 have been found in multiple biological processes including angiogenesis, apoptosis, activation of TGF-beta and Immune regulation. As such, TSP-1 is designated a multifunctional protein.
Overexpression of TSPs in tumor cells results in reduced angiogenesis. Inhibitory peptides and fragments of TSP1 bind to CD36, leading to the expression of FAS ligand (FasL), which activates the expression of Fas. This leads to the activation of caspases and apoptosis of the cell.
Lectin-like action of platelets
Thrombospondin (TSP) is a glycoproteins secreted from the alpha-granules of platelets upon activation. In the presence of divalent cations, the secreted protein binds to the surface of the activated platelets and is responsible for the endogenous lectin-like activity associated with activated platelets. Like hG3 it plays a critical role in endothelial adhesion to the cellular matrix.
- Blood 1985 Mar;65(3):615-9
- Biochemistry 1985 Jun 18;24(13):3128-34