Expert Reviews in Molecular Medicine

 



Review Article

Metalloproteinases and their inhibitors in angiogenesis


Marc A. Lafleur a1, Madeleine M. Handsley a2 and Dylan R. Edwards a2c1
a1 St Vincent's Institute of Medical Research, 9 Princes Street, Fitzroy, Victoria 3065, Australia.
a2 School of Biological Sciences, University of East Anglia, Norwich, NR4 7TJ, UK.

Abstract

Angiogenesis, the formation of new blood vessels from the pre-existing vasculature, is an integral part of physiological processes such as embryonic development, the female reproductive cycle and wound healing. Angiogenesis is also central to a variety of pathologies including cancer, where it is recognised as being crucial for the growth of solid tumours. Matrix metalloproteinases (MMPs) are a family of soluble and membrane-anchored proteolytic enzymes that can degrade components of the extracellular matrix (ECM) as well as a growing number of modulators of cell function. Several of the MMPs, most notably MMP-2 and -9 and membrane-type-1 MMP (MT1-MMP), have been linked to angiogenesis. Potential roles for these proteases during the angiogenic process include degradation of the basement membrane and perivascular ECM components, liberation of angiogenic factors, production of endogenous angiogenic inhibitors, and the unmasking of cryptic biologically relevant sites in ECM components. This review brings together what is currently known about the functions of the MMPs and the closely related adamalysin metalloproteinase (ADAM) family in angiogenesis, and discusses how this information might be useful in manipulation of the angiogenic process, with a view to controlling aberrant neovascularisation.


Key Words: angiogenesis; MMP; TIMP; ADAM; extracellular matrix; endothelial cells; matrix metalloproteinase; adamalysin metalloproteinase.

Correspondence:
c1 School of Biological Sciences, University of East Anglia, Norwich, NR4 7TJ, UK. Tel: +44 (0)1603 592184; Fax: +44 (0)1603 592250; E-mail: dylan.edwards@uea.ac.uk