Interactions between thrombospondin and the small proteoglycan decorin: interference with cell attachment.

Decorin, a ubiquitous small interstitial dermatan sulfate proteoglycan, interacts with several extracellular matrix components, e.g., with type I collagen and fibronectin. Using a solid phase assay it is shown that the intact proteoglycan as well as its glycosaminoglycan-free core protein exhibits with KD values of about 5 nM and 2 nM, respectively, high affinity binding also to thrombospondin. However, the polysaccharide chain was required for an interaction with Sepharose-bound thrombospondin and served itself as ligand. In light of the results of binding studies with an N-terminal heparin-binding fragment of thrombospondin it is concluded that several structural features of thrombospondin and of decorin contribute to the mutual interaction of the two macromolecules. Thrombospondin substrata allowed attachment but prevented spreading of human skin fibroblasts. The addition of decorin or of its glycosaminoglycan-free core protein led to a considerable delay of cell attachment on a thrombospondin substrate. The strength of cell attachment appeared to be reduced. These data support the antiadhesive role of decorin regardless of whether subsequent cell spreading is supported or not.