The membrane-type MMPs (MT-MMPs) are characterized by the presence of a transmembrane domain in the C terminus
12 that anchors these enzymes to the cell membranes.
32 The soluble forms of the MT-MMPs have recently been shown to be present in human induced sputum, bronchoalveolar lavage fluid, and gingival crevicular fluid.
21 24 The MT1-MMP (MMP-14) is a potent cell-surface activator of pro-MMP-2.
33 This cascade on the cell surface has been shown to be involved not only in the invasive and metastatic behavior of various cancers but also in human lung emphysema, asthma, and bronchiectasis.
24 34 Furthermore, MT1-MMP shows activity against a number of ECM components, including collagen I-III, gelatin, fibronectin, aggrecan, tenascin, nidogen, and perlecan.
35 Knockout mice without MT1-MMP, but with normal MMP-2 activity, exhibit dwarfism and have arthritis, osteopenia, and fibrosis of soft tissues.
36 Furthermore, evidence for an independent and pivotal role for MT1-MMP in connective tissue metabolism and angiogenesis has been presented.
36 Taken together, MT1-MMP is likely to play a dual role in stromal degradation and ECM remodeling during wound healing by activating other MMPs such as MMP-2
33 and -13
37 or by digesting various ECM components. Expression of MT1-MMP mRNA by stromal keratocytes or, more rarely, in the basal epithelial cells has been shown in both normal and wounded rat corneas.
38 Similarly, MT1-MMP mRNA was recently shown in stromal and epithelial cells of human corneas.
39 Analysis of MT1-MMP immunoreactivity revealed that it is located in the epithelial cell surface. It has also been suggested that in pterygia, MT1-MMP is responsible for the cleavage of fibrillar collagen in Bowman’s layer.
40