Discovery of Type IV Collagen Non-collagenous Domains as Novel Integrin Ligands and Endogenous Inhibitors of Angiogenesis
This extract was created in the absence of an abstract.
Excerpt
Type IV collagen is a major constituent of all mammalian basement membranes, including basement membranes of the vasculature. Type IV collagen is an ancientmatrix scaffold, and it is one of the two collagens presentin Caenorhabditis elegans and thus is ~600 million yearsold. Type IV collagen forms a spider web-like suprastructure that interacts with other components ofmolecules such as laminins, perlecans, and nidogen (entactin) to form a highly cross-linked and insoluble basement membrane usually present on the basolateral aspectof various cells. Type IV collagen interacts with cells viaadhesion molecules such as integrins, and these interactions are considered important for establishing a productive cell–matrix interaction and subsequent intracellularsignaling. The significance of type IV collagen in the regulation of angiogenesis has been studied for more than 15years now, and whereas the original work focused on positive regulation, in recent years, type IV collagen hasbeen identified as an important negative regulator of angiogenesis, potentially mediated by integrins. Degradation of type IV collagen can occur during various physiological and pathological processes that generate smallercollagen-derived fragments. These degradation fragments are likely involved in bioactivities differing fromtheir original intact type IV collagen molecule. This review highlights the properties of type IV collagen degradation products and, in particular, describes the discoveries of arresten, canstatin, and tumstatin as novel integrinligands and inhibitors of angiogenesis...
