Abstract
This chapter provides an overview on the role of thrombospondins (TSPs) in cancer. TSPs are a family composed of five highly conserved structurally related ECM proteins. TSP-1 and -2 are homotrimers, whereas TSPs-3, -4, and -5 form pentamers. The TSP-1 monomer is deficient in cell attachment and spreading properties compared with the TSP-1 integral unit. These activities require the carboxy (C)-terminal TSP repeats. The monomeric TSP-1 has several domains that include an amino (N)-terminal globular domain, an oligomerization domain, von Willebrand factor type C pro-collagen homology domain and three types of thrombospondin repeat (TSR) domains. There are three properdin type 1 domains, which possess specific ligand-binding property, three EGF-like type 2, 13 calcium binding type 3 repeats, and a globular domain at the C terminus. TSR domains occur with varying numbers of copies in many proteins. They occur in the secreted or in the extracellular region of the protein. They seem to be essential for the functions of cell migration, tissue remodeling, and signaling subserved by TSPs. They are believed to act as adhesion sites and protein- and glycosaminoglycan-binding site receptors and they also participate in the anti-angiogenic function of TSP. A specific TSR sequence (CSVTCG, cys-ser-val-thr-cys-gly) and possibly sequences flanking this are identified with the inhibition of angiogenesis and implicated with TSP-1 binding to CD36 receptors that occur on endothelial cells, a process that might bring about endothelial-cell apoptosis leading to the inhibition of angiogenesis.
Published Version
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