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 alpha 3 beta 1 and alpha 6 beta 1 on microvascular endothelial cells (EC) and Integrin alpha 4 beta 1 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).