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Biological functions of collagen fragments

Type IV, XV and XVIII collagens are key architectural components of basement membranes. Recent work, however, indicates that they are also important sources of biological mediators: during extracellular matrix remodelling, proteolysis of these collagens generates fragments that regulate a variety of processes, including cell proliferation, migration and apoptosis. In a Commentary on p. 4201, Nathalie Ortega and Zena Werb review studies that have shed light on the nature of such fragments, which include endostatin, arresten and tumstatin. The fragments derive from the non-collagenous C-terminal (NC1) domains of the collagens and bind to cell surface receptors and matrix proteins. Tumstatin, for example, binds to integrin vß3; this has an anti-angiogenic effect, increasing apoptosis of endothelial cells. Endostatin is also an effective inhibitor of angiogenesis — hence its potential as an anti-tumour therapy. In general, the soluble NC1 fragments appear to have dominant negative roles, antagonizing the promigratory, proliferative activities of their immobilized counterparts. The balance between these positive and negative activities could therefore provide a finely tuned regulatory mechanism for control of invasive processes such as angiogenesis and branching morphogenesis.

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New functional roles for non-collagenous domains of basement membrane collagens

Nathalie Ortega and Zena Werb
JCS 2002 115: 4201-4214. [Abstract] [Full Text]  

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in JCS Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Search for Related Content Social Bookmarking                         What's this?