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Metalloproteinases and their inhibitors in tumor angiogenesis
Author(s) -
Handsley Madeleine M.,
Edwards Dylan R.
Publication year - 2005
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.20945
Subject(s) - angiogenesis , matrix metalloproteinase , basement membrane , extracellular matrix , proteases , microbiology and biotechnology , biology , adamts , matrix metalloproteinase inhibitor , cancer research , proteolytic enzymes , immunology , metalloproteinase , thrombospondin , biochemistry , enzyme
Angiogenesis is the process by which new blood vessels are formed from preexisting vasculature. It is an essential feature of the female reproductive cycle, embryonic development and wound repair. Angiogenesis has also been identified as a causal or contributing factor in several pathologies, including cancer, where it is a rate‐limiting step during tumor progression. 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, in particular the gelatinases 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, unmasking of cryptic biologically relevant sites in ECM components, modulation of angiogenic factors and production of endogenous angiogenic inhibitors. This review brings together what is currently known about the functions of the MMPs and the closely related ADAM ( a d isintegrin a nd m etalloproteinase domain) and ADAMTS ( a d isintegrin a nd m etalloproteinase with t hrombo s pondin motifs) families in angiogenesis and considers how this information might be useful in manipulation of the angiogenic process, with a view to constraining tumor progression. © 2005 Wiley‐Liss, Inc.