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Cell Mol Life Sci. 2004 Jul;61(14):1826-33.

Activity of MMP-19 inhibits capillary-like formation due to processing of nidogen-1.

Author information

1
Institute of Biochemistry, Christian-Albrechts-Universit├Ąt zu Kiel, Olshausenstr. 40, 24098, Germany.

Abstract

Matrix metalloproteinase 19 (MMP-19) is able to process various proteins of the basement membrane. To investigate the impact of MMP-19 activity on endothelial cells in the context of tumor extracellular matrix (ECM), we treated Matrigel matrix with an active recombinant MMP-19 and analyzed its effect on capillary-like formation. Human microvascular endothelial cells (HMEC-1) could not form capillary-like formation on Matrigel treated with recombinant MMP-19. Analyzing the Matrigel proteins, we found that MMP-19 preferentially cleaved nidogen-1. The cleavage site of nidogen-1 was mapped to Thr867-Leu868. This cleavage separates the G3 globular domain containing the binding site for the gamma1 chain of laminin-1 and collagen IV and thus abolishes the capacity of nidogen-1 to cross-link ECM proteins. Anti-nidogen antibodies directed against the G3 domain of nidogen-1 inhibited the capillary-like structure formation to a similar extent as MMP-19. Since nidogen-1 is thought to stabilize microvessels, MMP-19 might be one of the enzymes that interferes with stabilization or maturation of nascent vasculature.

PMID:
15241558
DOI:
10.1007/s00018-004-4105-0
[Indexed for MEDLINE]
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