Article (Scientific journals)
New and Paradoxical Roles of Matrix Metalloproteinases in the Tumor Microenvironment.
Noël, Agnès; Gutierrez-Fernandez, A; Sounni, Nor Eddine et al.
2012In Frontiers in Pharmacology, 3 (140), p. 1
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Keywords :
matrix metalloproteinases; ADAM; cancer; tumor; microenvironment
Abstract :
[en] Processes such as cell proliferation, angiogenesis, apoptosis, or invasion are strongly influenced by the surrounding microenvironment of the tumor. Therefore, the ability to change these surroundings represents an important property through which tumor cells are able to acquire specific functions necessary for tumor growth and dissemination. Matrix metalloproteinases (MMPs) constitute key players in this process, allowing tumor cells to modify the extracellular matrix (ECM) and release cytokines, growth factors, and other cell-surface molecules, ultimately facilitating protease-dependent tumor progression. Remodeling of the ECM by collagenolytic enzymes such as MMP1, MMP8, MMP13, or the membrane-bound MT1-MMP as well as by other membrane-anchored proteases is required for invasion and recruitment of novel blood vessels. However, the multiple roles of the MMPs do not all fit into a simple pattern. Despite the pro-tumorigenic function of certain metalloproteinases, recent studies have shown that other members of these families, such as MMP8 or MMP11, have a protective role against tumor growth and metastasis in animal models. These studies have been further expanded by large-scale genomic analysis, revealing that the genes encoding metalloproteinases, such as MMP8, MMP27, ADAM7, and ADAM29, are recurrently mutated in specific tumors, while several ADAMTSs are epigenetically silenced in different cancers. The importance of these proteases in modifying the tumor microenvironment highlights the need for a deeper understanding of how stroma cells and the ECM can modulate tumor progression.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Noël, Agnès ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie cellulaire et moléculaire appliquée à l'homme
Gutierrez-Fernandez, A
Sounni, Nor Eddine  ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie cellulaire et moléculaire appliquée à l'homme
Behrendt, N
Maquoi, Erik  ;  Université de Liège - ULiège > Département des sciences cliniques > Labo de biologie des tumeurs et du développement
Lund, IK
Cal, S
Hoyer-Hansen, G
Lopez-Otin, C
Language :
English
Title :
New and Paradoxical Roles of Matrix Metalloproteinases in the Tumor Microenvironment.
Publication date :
2012
Journal title :
Frontiers in Pharmacology
ISSN :
1663-9812
Publisher :
Frontiers, Switzerland
Volume :
3
Issue :
140
Pages :
1
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 05 September 2012

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