Recombinant Human Thrombospondin-2 Protein, CF

Thrombospondin-2 (TSP-2) is a 150 kDa calcium-binding protein that modulates cellular interactions with extracellular matrix. Thrombospondin-1 and -2 constitute subgroup A thrombospondin family members and form disulfide-linked homotrimers, whereas Thrombospondin-3, -4, and -5/COMP constitute subgroup B and form homopentamers (1‑4). The human TSP-2 cDNA encodes a 1172 amino acid (aa) precursor that includes an 18 aa signal sequence followed by an N-terminal heparin‑binding domain, an oligomerization motif, one vWF-C domain, three TSP type-1 repeats, three EGF-like repeats, seven TSP type-3 repeats, and a lectin-like TSP C‑terminal domain (5). Human TSP-2 shares 88‑90% aa sequence identity with bovine, mouse, and rat TSP-2. Within the TSP type-3 repeats and TSP C-terminal domain, human TSP-2 shares 80% aa sequence identity with human TSP-1 and approximately 60% aa sequence identity with human TSP-3, -4, and -5/COMP. TSP-2 regulates collagen matrix formation by altering fibroblast behavior during development and in areas of tissue remodeling in the adult (6, 7). Trimerization of TSP-2 is required for the calcium-dependent cell attachment and spreading functions, while the heparin‑binding domain is responsible for the destabilization of focal adhesion sites (8‑10). The heparin‑binding domain also mediates binding to Integrins alpha3 beta1 and alpha6 beta1 on microvascular endothelial cells (EC) and Integrin alpha4 beta1 on large blood vessel EC (11, 12). A fragment of TSP-2 (heparin‑binding domain, oligomerization motif, and vWF-C domain) promotes EC survival, proliferation, and chemotaxis (11). Inclusion of the three TSP type-1 domains results in a molecule that inhibits VEGF-induced EC migration and vascular tube formation (13, 14). In vivo, full length TSP-2 blocks tumor angiogenesis and induces vascular EC apoptosis (13, 15). HPRG functions as an apparent decoy receptor by preventing interaction of TSP-2 with CD36 on macrophages and microvasculature EC (14). TSP-2 also binds MMP-2 and facilitates MMP-2 clearance by the scavenger receptor LRP (16).