Thrombospondin

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Thrombospondins (TSP) are secreted proteins with the ability to inhibit angiogenesis.

[edit] Importance

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.

TSP-1 has multiple receptors, among which CD36, CD47 and integrins are of particular note.

TSP-1 acts to inhibit angiogenesis, inhibiting the proliferation and migration of endothelial cells by interactions with CD36 expressed on their surface of these cells. 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. Overexpression of TSP-1 in tumor cells is considered as a good prognosis, and TSP-1 has recently gone into trials as a cancer therapy.