Discovery of type IV collagen non-collagenous domains as novel integrin ligands and endogenous inhibitors of angiogenesis

R Kalluri - Cold Spring Harbor symposia on quantitative …, 2002 - symposium.cshlp.org
Cold Spring Harbor symposia on quantitative biology, 2002symposium.cshlp.org
Cold Spring Harbor Symposia on Quantitative Biology, Volume LXVII.© 2002 Cold Spring
Harbor Laboratory Press 0-87969-678-8/02. 255 membranes (BM) are a specialized
meshwork of extracellular matrix (ECM) molecules, which are crucial for the development of
metazoans (Paulsson 1992; Yurchenco and O'Rear 1994; Timpl 1996; Li et al. 2002). Along
with providing structural support, VBM is also speculated to modulate cell behavior. Its
remodeling, as defined by VBM synthesis and degradation, generates disparate signals to …
Cold Spring Harbor Symposia on Quantitative Biology, Volume LXVII.© 2002 Cold Spring Harbor Laboratory Press 0-87969-678-8/02. 255 membranes (BM) are a specialized meshwork of extracellular matrix (ECM) molecules, which are crucial for the development of metazoans (Paulsson 1992; Yurchenco and O’Rear 1994; Timpl 1996; Li et al. 2002). Along with providing structural support, VBM is also speculated to modulate cell behavior. Its remodeling, as defined by VBM synthesis and degradation, generates disparate signals to the cells (Bergers et al. 2000; Colorado et al. 2000; Egeblad and Werb 2002). In a general sense, BM are thin layers of a specialized ECM that provide the supporting structure on which epithelial and endothelial cells grow and reside. In addition, they are closely associated with muscle fibers, fat mass, and peripheral nerves. BM are composed of about 50 different macromolecules; the most abundant molecules are type IV collagen, laminin, heparan sulfate proteoglycans (perlecans), fibronectin, and nidogen (Fig. 1A). BM molecules are quite large in molecular size and have the capacity to self-aggregate to form higher-order structures (Yurchenco and O’Rear 1994; Li et al. 2002; Yurchenco et al. 2002). Type IV collagen protomers self-associate via their ends and their middle triple helical regions to form a spider web scaffold-like structure that interacts with the laminin network, which by itself also has the ca-
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