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

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

Research output: Contribution to journalArticle

128 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Metalloproteases
Matrix Metalloproteinases
Epithelial Cells
Cells
Neoplasms
Matrix Metalloproteinase 7
Vitronectin
Gene encoding
Cloning
Extracellular Matrix Proteins
Substrate Specificity
Gene Library
Fibronectins
Introns
Fibrinogen
Names
Cysteine
Organism Cloning
Tumors
Prostate

Keywords

  • Carcinomas
  • Collagenase
  • Epithelial cancer
  • Gelatinase
  • MMP

ASJC Scopus subject areas

  • Biochemistry

Cite this

Characterization of matrix metalloproteinase-26, a novel metalloproteinase widely expressed in cancer cells of epithelial origin. / Marchenko, G. N.; Ratnikov, B. I.; Rozanov, Dmitri; Godzik, A.; Deryugina, E. I.; Strongin, A. Y.

In: Biochemical Journal, Vol. 356, No. 3, 15.06.2001, p. 705-718.

Research output: Contribution to journalArticle

Marchenko, G. N. ; Ratnikov, B. I. ; Rozanov, Dmitri ; Godzik, A. ; Deryugina, E. I. ; Strongin, A. Y. / Characterization of matrix metalloproteinase-26, a novel metalloproteinase widely expressed in cancer cells of epithelial origin. In: Biochemical Journal. 2001 ; Vol. 356, No. 3. pp. 705-718.
@article{727ba04348464ae08e6ede64b306bbb0,
title = "Characterization of matrix metalloproteinase-26, a novel metalloproteinase widely expressed in cancer cells of epithelial origin",
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; Ur{\'i}a and L{\'o}pez-Ot{\'i}n (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].",
keywords = "Carcinomas, Collagenase, Epithelial cancer, Gelatinase, MMP",
author = "Marchenko, {G. N.} and Ratnikov, {B. I.} and Dmitri Rozanov and A. Godzik and Deryugina, {E. I.} and Strongin, {A. Y.}",
year = "2001",
month = "6",
day = "15",
doi = "10.1042/0264-6021:3560705",
language = "English (US)",
volume = "356",
pages = "705--718",
journal = "Biochemical Journal",
issn = "0264-6021",
publisher = "Portland Press Ltd.",
number = "3",

}

TY - JOUR

T1 - Characterization of matrix metalloproteinase-26, a novel metalloproteinase widely expressed in cancer cells of epithelial origin

AU - Marchenko, G. N.

AU - Ratnikov, B. I.

AU - Rozanov, Dmitri

AU - Godzik, A.

AU - Deryugina, E. I.

AU - Strongin, A. Y.

PY - 2001/6/15

Y1 - 2001/6/15

N2 - 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].

AB - 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].

KW - Carcinomas

KW - Collagenase

KW - Epithelial cancer

KW - Gelatinase

KW - MMP

UR - http://www.scopus.com/inward/record.url?scp=0035875151&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035875151&partnerID=8YFLogxK

U2 - 10.1042/0264-6021:3560705

DO - 10.1042/0264-6021:3560705

M3 - Article

C2 - 11389678

AN - SCOPUS:0035875151

VL - 356

SP - 705

EP - 718

JO - Biochemical Journal

JF - Biochemical Journal

SN - 0264-6021

IS - 3

ER -