Extracellular matrix disassembly is the degradation of the matrix components by proteases such as matrix metalloproteinases, and is a key step in normal physiological functions such as embryonic development and tissue remodeling, as well as in pathological conditions such as cancer progression.
Variations in MMP structure exist (see Figure: Variations in MMP structure at bottom), with the addition or loss of certain domains (as reviewed in ). For example; MMP7 and MMP26 lack the hemopexin domain. MMP2 and MMP9 have additional fibronectin domain inserts within the catalytic domain. Membrane bound MMPs have additional membrane linkage domains, such as a GPI (glycosylphosphatidylinositol) anchor in the case of MMP14, MMP15, MMP16 and MMP24.
MMPs are produced as inactive precursors which are exposed to the extracellular milieu either via secretion or translocation to the membrane. Once exposed to the extracellular environment they are activated through proteolytic cleavage of the N terminal autoinhibitory domain.
Cleavage is carried out by a range of different proteases including the MMPs themselves, as well as tissue proteases such as tryptase, plasmin and kallikrein . Following activation, MMPs are able to digest various ECM components including a host of collagen types (I-V, VII, X, XI), gelatin, laminin, basement membrane proteins entactin and perlecan and ECM glycoproteins such as tenascin . Active MMPs are involved in a wide range of cellular processes including; tissue remodeling, cell survival, immune cell migration and cancer pathology .