Metalloproteinases and their inhibitors in angiogenesis.
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.
Lafleur
Marc A
MA
St Vincent's Institute of Medical Research, 9 Princes Street, Fitzroy, Victoria 3065, Australia. mlafleur@medstv.unimelb.edu.au
Handsley
Madeleine M
MM
Edwards
Dylan R
DR
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000818:Animals; D001808:Blood Vessels / Q000166:cytology / Q000473:pathology / Q000502:physiology; D002455:Cell Division / Q000187:drug effects; D004791:Enzyme Inhibitors; D006801:Humans; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000378:metabolism; D045726:Metalloproteases / Q000378:metabolism*; D009369:Neoplasms / Q000098:blood supply / Q000188:drug therapy; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D011480:Protease Inhibitors / Q000494:pharmacology*; D014945:Wound Healing
D020533:Angiogenesis Inhibitors; D004791:Enzyme Inhibitors; D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors; D045726:Metalloproteases; D020782:Matrix Metalloproteinases