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

G. N. Marchenko, B. I. Ratnikov, D. V. Rozanov, A. Godzik, E. I. Deryugina, A. Y. Strongin

Research output: Contribution to journalArticle

129 Scopus citations

Abstract

Identification of expanding roles for matrix metalloproteinases (MMPs) in complex regulatory processes of tissue remodelling has stimulated the search for genes encoding proteinases with unique functions, regulation and expression patterns. By using a novel cloning strategy, we identified three previously 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 of a novel MMP, MMP-26. Our findings show that MMP-26 is specifically expressed in cancer cells of epithelial origin, including carcinomas of lung, prostate and breast. Several unique structural and regulatory features, including an unusual 'cysteine-switch' motif, discriminate broadspectrum MMP-26 from most other MMPs. MMP-26 efficiently cleaves fibrinogen and extracellular matrix proteins, including fibronectin, vitronectin and denatured collagen. Protein sequence, minimal modular domain structure, exon-intron mapping and computer modelling demonstrate similarity between MMP-26 and MMP-7 (matrilysin). However, substrate specificity and transcriptional regulation, as 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 trivial name for MMP-26. Our observations suggest an important specific function for MMP-26 in tumour progression and angiogenesis, and confirm and extend the recent findings of other authors [Park, Ni, Gerkema, Liu, Belozerov and Sang (2000) J. Biol. Chem. 275, 20540-20544; Uría and López-Otín (2000) Cancer Res. 60, 4745-4751; de Coignac, Elson, Delneste, Magistrelli, Jeannin, Aubry, Berthier, Schmitt, Bonnefoy and Gauchat (2000) Eur. J. Biochem. 267, 3323-3329].

Original languageEnglish (US)
Pages (from-to)705-718
Number of pages14
JournalBiochemical Journal
Volume356
Issue number3
DOIs
StatePublished - Jun 15 2001

Keywords

  • Carcinomas
  • Collagenase
  • Epithelial cancer
  • Gelatinase
  • MMP

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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