Characterization of matrix metalloproteinase-26, a novel metalloproteinasewidely expressed in cancer cells of epithelial origin

Identification of expanding roles for matrix metalloproteinases (MMPs) in c omplex regulatory processes of tissue remodelling has stimulated the search for genes encoding proteinases with unique functions, regulation and expre ssion patterns. By using a novel cloning strategy, we identified three prev iously unknown human MMPs, i.e. MMP-21, MMP-26 and MMP-28, in comprehensive gene libraries. The present study is focused on the gene and the protein o f a novel MMP, MMP-26. Our findings show that MMP-26 is specifically expres sed in cancer cells of epithelial origin, including carcinomas of lung, pro state and breast. Several unique structural and regulatory features, includ ing an unusual 'cysteine-switch' motif, discriminate broad-spectrum MMP-26 from most other MMPs. MMP-26 efficiently cleaves fibrinogen and extracellul ar matrix proteins, including fibronectin, vitronectin and denatured collag en. Protein sequence, minimal modular domain structure, exon-intron mapping and computer modelling demonstrate similarity between MMP-26 and MMP-7 (ma trilysin). However, substrate specificity and transcriptional regulation, a s well as the functional role of MMP-26 and MMP-7 in cancer. are likely to be distinct. Despite these differences, matrilysin-2 may be a suitable triv ial name for MMP-26. Our observations suggest an important specific functio n for MMP-26 in tumour progression and angiogenesis, and confirm and extend the recent findings of other authors [Park, Ni, Gerkema, Liu, Belozerov an d Sang (2000) J. Biol. Chem. 275, 20540-20544; Uria and Lopez-Otin (2000) C ancer Res. 60, 4745-4751; de Coignac, Elson, Delneste, Magistrelli, Jeannin , Aubry, Berthier, Schmitt, Bonnefoy and Gauchat (2000) fur. J. Biochem. 26 7, 3323-3329].