Article (Scientific journals)
Targeting a single function of the multifunctional matrix metalloprotease MT1-MMP. Impact on lymphangiogenesis.
Ingvarsen, Signe; Porse, Astrid; Erpicum, Charlotte et al.
2013In Journal of Biological Chemistry, sous presse
Peer Reviewed verified by ORBi
 

Files


Full Text
Ingvarsen SJ. Biol. Chem.-2013.pdf
Publisher postprint (2.95 MB)
Request a copy

All documents in ORBi are protected by a user license.

Send to



Details



Keywords :
MMP-14; membrane type matrix metalloprotease,; gelatinase; lymphangiogenesis; proenzyme activation; inhibitory monoclonal antibody,; monoclonal antibody therapy
Abstract :
[en] The group of matrix metalloproteases (MMPs) is responsible for multiple processes of extracellular matrix remodeling in the healthy body but also for matrix and tissue destruction during cancer invasion and metastasis. The understanding of the contributions from each individual MMP, both in healthy and pathological events, has been complicated by the lack of specific inhibitors and the fact that some of the potent MMPs are multifunctional enzymes. These factors have also hampered the setup of therapeutic strategies targeting MMP activity. A tempting target is the membrane-associated MT1-MMP which has well-documented importance in matrix degradation but which takes part in more than one pathway in this regard. In this report, we describe the selective targeting of a single function of this enzyme by means of a specific monoclonal antibody against MT1-MMP, raised in an MT1-MMP knock-out mouse. The antibody blocks the enzyme ability to activate proMMP-2 without interfering with the collagenolytic function or the general proteolytic activity of MT1-MMP. Using this antibody, we have shown that the MT1-MMP-catalyzed activation of proMMP- 2 is involved in the outgrowth of cultured lymphatic endothelial cells in a collagen matrix in vitro, as well as in lymphatic vessel sprouting assayed ex vivo. This is the first example of the complete inactivation of a single function of a multifunctional MMP and the use of this strategy to pursue its role.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Ingvarsen, Signe
Porse, Astrid
Erpicum, Charlotte ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie cellulaire et moléculaire appliquée à l'homme
Maertens, Ludovic ;  Université de Liège - ULiège > Département des sciences cliniques > Labo de biologie des tumeurs et du développement
Jurgensen, Henrik J.
Madsen, Daniel H.
Melander, Maria C.
Gardsvoll, Henrik
Hoyer-Hansen, Gunilla
Noël, Agnès ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie cellulaire et moléculaire appliquée à l'homme
Holmbeck, Kenn
Engelholm, Lars H.
Behrendt, Niels
More authors (3 more) Less
Language :
English
Title :
Targeting a single function of the multifunctional matrix metalloprotease MT1-MMP. Impact on lymphangiogenesis.
Publication date :
2013
Journal title :
Journal of Biological Chemistry
ISSN :
0021-9258
eISSN :
1083-351X
Publisher :
American Society for Biochemistry and Molecular Biology, Baltimore, United States - Maryland
Volume :
sous presse
Peer reviewed :
Peer Reviewed verified by ORBi
European Projects :
FP7 - 201279 - MICROENVIMET - Understanding and fighting metastasis by modulating the tumour microenvironment through interference with the protease network.
Funders :
CE - Commission Européenne [BE]
Available on ORBi :
since 21 May 2013

Statistics


Number of views
56 (11 by ULiège)
Number of downloads
1 (1 by ULiège)

Scopus citations®
 
48
Scopus citations®
without self-citations
44
OpenCitations
 
46

Bibliography


Similar publications



Contact ORBi