title: Activity of MMP-19 inhibits capillary-like formation due to processing of nidogen-1.
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.
authors.affiliation: Institute of Biochemistry, Christian-Albrechts-Universität zu Kiel, Olshausenstr. 40, 24098, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Titz
authors.forename: S
authors.initials: S
authors.lastname: Dietrich
authors.forename: T
authors.initials: T
authors.lastname: Sadowski
authors.forename: C
authors.initials: C
authors.lastname: Beck
authors.forename: A
authors.initials: A
authors.lastname: Petersen
authors.forename: R
authors.initials: R
authors.lastname: Sedlacek
mesh_terms: D002455:Cell Division / Q000502:physiology; D004727:Endothelium / Q000378:metabolism; D006801:Humans; D053505:Matrix Metalloproteinases, Secreted; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism*; D008666:Metalloendopeptidases / Q000378:metabolism*; D009389:Neovascularization, Pathologic / Q000201:enzymology / Q000276:immunology / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D014407:Tumor Cells, Cultured
chemical_list: D008562:Membrane Glycoproteins; C029967:nidogen; D053505:Matrix Metalloproteinases, Secreted; D008666:Metalloendopeptidases; C108362:matrix metalloproteinase 19