Thrombospondin-1

Thrombospondin-1 (TSP-1) was first isolated from platelets that had been stimulated with thrombin and so was designated 'thrombin-sensitive protein'. Since its first recognition, TSP-1 has been found to participate 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 is an antiangiogenic, 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 its specific receptor Fas. This leads to the activation of caspases and apoptosis of the cell. Since tumors overexpressing TSP-1 typically grow slower, exhibit less angiogenesis, and have fewer metastases, TSP1 is an attractive target for cancer treatment. Because TSP1 is extremely large (~120 kDa monomer), not very abundant, and exerts multiple actions, its clinical usefulness is questionable. However, small-molecules based on a CD36-binding peptide sequence from TSP1 are being tested. One analog, ABT-510, exhibits potent proapoptotic activity in cultured cells, while clinically it is very well tolerated with therapeutic benefits reported against several malignancies. ABT-510 is being evaluated in clinical trials for the treatment of several types of cancer.

Swiss-Prot Accession Number: P07996


 
 
Publications
Dendritic cell immunotherapy followed by cART interruption during HIV-1 infection induces plasma protein markers of cellular immunity and neutrophil recruitment (2018) van den Ham HJ, Cooper J, Tomasik J, Bahn S, Aerts J, Oseterhaus A, Gruters R, Andeweg A PLoS One
Effects of Acute Endurance Exercise on Plasma Protein Profiles of Endurance-Trained and Untrained Individuals over Time (2016) Schild M, Eichner G, Beiter T, Zuegel M, Niess AM, Steinacker JM, Mooren FC Mediators of Inflammation
Sjögren’s Syndrome Patients with Ectopic Germinal Centers Present with a Distinct Salivary Proteome (2016) Delaleu N, Mydel P, Brun JG, Jonsson MV, Alimonti A, Jonsson R Rheumatology
Variation in Serum Biomarkers with Sex and Female Hormonal Status: Implications for Clinical Tests (2016) Ramsey JM, Cooper JD, Penninx BWJH, Bahn S Scientific Reports
Allogeneic mesenchymal stem cell infusion for the stabilization of focal segmental glomerulosclerosis (2013) Belingheri M, Lazzari L, Parazzi V, Groppali E, Biagi E, Gaipa G, Giordano R, Rastaldi MP, Croci D, Biondi A, Rebulla P, Edefonti A, Ghio L Biologicals. 2013 Oct 14. pii: S1045-1056(13)00111-5. doi: 10.1016/j.biologicals.2013.09.004
Identification of blood-based molecular signatures for prediction of response and relapse in schizophrenia patients (2012) Schwarz E, Guest PC, Steiner J, Bogerts B, Bahn S Translational Psychiatry (2012) 2, e82