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Metalloproteinase-dependent tubulogenesis

The formation of new blood vessels is critical for development, wound healing and tumour progression. A variety of angiogenic factors, including vascular endothelial growth factor (VEGF) and fibroblast growth factor 2 (FGF-2), regulate the process, and matrix metalloproteinases (MMPs) are thought to participate in the matrix remodelling required. Dylan Edwards and co-workers have examined the interplay between these proteins during remodelling of endothelial cells in 3D fibrin matrices — a useful model system that, unlike 2D cultures, mimics the microenvironment at sites of vascular injury (see p. 3427). The authors observe that endothelial cells undergo tubulogenesis when cultured in these matrices, showing that tubulogenesis is enhanced by VEGF, FGF-2 and hepatocyte growth factor (HGF/SCF) and accompanied by upregulation of several MMP genes. They also find that the MMP inhibitors TIMP-2 and TIMP-4, which target membrane-type MMPs (MT-MMPs), block VEGF/FGF-2-stimulated tubulogenesis but that inhibitors of soluble MMPs (e.g. MMP-2) do not. Edwards and co-workers conclude that MT-MMPs represent a subgroup of MMPs crucial for angiogenesis and therefore constitute enzymes that could be selectively targeted by antiangiogenic therapies.

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Endothelial tubulogenesis within fibrin gels specifically requires the activity of membrane-type-matrix metalloproteinases (MT-MMPs)

Marc A. Lafleur, Madeleine M. Handsley, Vera Knäuper, Gillian Murphy, and Dylan R. Edwards
JCS 2002 115: 3427-3438. [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?