Cellular and Molecular Life Sciences CMLS

, Volume 61, Issue 14, pp 1826–1833

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

  • B. Titz
  • S. Dietrich
  • T. Sadowski
  • C. Beck
  • A. Petersen
  • R. Sedlacek
Research Article

DOI: 10.1007/s00018-004-4105-0

Cite this article as:
Titz, B., Dietrich, S., Sadowski, T. et al. CMLS, Cell. Mol. Life Sci. (2004) 61: 1826. doi:10.1007/s00018-004-4105-0

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 γ1 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.

Extracellular matrixmatrix metalloproteinaseangiogenesis

Copyright information

© Birkhäuser-Verlag Basel 2004

Authors and Affiliations

  • B. Titz
    • 1
  • S. Dietrich
    • 1
  • T. Sadowski
    • 1
  • C. Beck
    • 1
  • A. Petersen
    • 2
  • R. Sedlacek
    • 1
  1. 1.Institute of BiochemistryChristian-Albrechts-Universität zu KielKielGermany
  2. 2.Biochemische und Molekulare AllergologieForschungszentrum BorstelBorstelGermany