Thrombospondin-1 (TSP1) is a homotrimeric glycoprotein and a member of the Thrombospondin family. It is encoded by the THBS1 gene. TSP1 is involved in cell-to-cell and cell-to-matrix interactions. It binds to various molecules, including fibrinogen, fibronectin, laminin, type V collagen, and integrins alpha-V/beta-1. TSP1 plays a crucial role in platelet aggregation, angiogenesis, and tumorigenesis. It acts as an inhibitor of neovascularization and tumorigenesis in healthy tissues. TSP1 interacts with numerous cell adhesion receptors, such as CD36, av integrins, b1 integrins, syndecan, and integrin-associated protein (IAP or CD47). Additionally, it interacts with proteases involved in angiogenesis, including plasminogen, matrix metalloproteinase, thrombin, cathepsin, and elastase. TSP1 exhibits both positive and negative modulatory effects on endothelial cell adhesion, motility, and growth. Recent studies have revealed that TSP1 binds to reelin receptors, ApoER2 and VLDLR, influencing neuronal migration in the rostral migratory stream.
Thrombospondin-1 is a large protein with a molecular mass ranging from 150 to 180 kDa. It is secreted as a disulfide-linked homotrimer, meaning it consists of three identical subunits linked by disulfide bonds . The protein contains several distinct domains, including:
Thrombospondin-1 is known for its role in modulating cell adhesion, motility, and growth. It interacts with a variety of cell adhesion receptors, including CD36, αv integrins, β1 integrins, syndecan, and integrin-associated protein (IAP or CD47) . Additionally, it interacts with numerous proteases involved in angiogenesis, such as plasminogen, urokinase, matrix metalloproteinase, thrombin, cathepsin, and elastase .
One of the key functions of thrombospondin-1 is its ability to inhibit neovascularization and tumorigenesis in healthy tissue. It has been shown to both positively and negatively modulate endothelial cell adhesion, motility, and growth . This dual role makes it a potential target for therapeutic applications in cancer treatment.
Recombinant human thrombospondin-1 is produced using various expression systems, including mouse myeloma cell lines and human embryonic kidney (HEK) 293 cells . The recombinant protein is typically purified to high levels of purity and is used in various research applications, including studies on cell migration, proliferation, and angiogenesis.
Recombinant thrombospondin-1 is often used in functional assays to study its binding ability and interactions with other proteins. For example, it has been shown to bind to recombinant human vascular endothelial growth factor (VEGF) in a functional ELISA .
Due to its role in modulating cell adhesion, motility, and growth, thrombospondin-1 has potential therapeutic applications in various fields, including cancer therapy, wound healing, and tissue engineering. Recombinant versions of thrombospondin-1 and its functional domains are being explored for their ability to inhibit tumor growth and angiogenesis .