title: Membrane-type 4 matrix metalloproteinase promotes breast cancer growth and metastases.
abstract: Membrane-type matrix metalloproteinases (MT-MMP) constitute a subfamily of six distinct membrane-associated MMPs. Although the contribution of MT1-MMP during different steps of cancer progression has been well documented, the significance of other MT-MMPs is rather unknown. We have investigated the involvement of MT4-MMP, a glycosylphosphatidylinositol-anchored protease, in breast cancer progression. Interestingly, immunohistochemical analysis shows that MT4-MMP production at protein level is strongly increased in epithelial cancer cells of human breast carcinomas compared with normal epithelial cells. Positive staining for MT4-MMP is also detected in lymph node metastases. In contrast, quantitative reverse transcription-PCR analysis reveals similar MT4-MMP mRNA levels in human breast adenocarcinomas and normal breast tissues. Stable transfection of MT4-MMP cDNA in human breast adenocarcinoma MDA-MB-231 cells does not affect in vitro cell proliferation or invasion but strongly promotes primary tumor growth and associated metastases in RAG-1 immunodeficient mice. We provide for the first time evidence that MT4-MMP overproduction accelerates in vivo tumor growth, induces enlargement of i.t. blood vessels, and is associated with increased lung metastases. These results identify MT4-MMP as a new putative target to design anticancer strategies.
authors.affiliation: Laboratory of Tumor and Development Biology, Centre de Recherche en Cancérologie Expérimentale, Center for Biomedical Integrative Genoproteomics, University of Liège, Belgium.
authors.forename: Vincent
authors.initials: V
authors.lastname: Chabottaux
authors.forename: Nor Eddine
authors.initials: NE
authors.lastname: Sounni
authors.forename: Caroline J
authors.initials: CJ
authors.lastname: Pennington
authors.forename: William R
authors.initials: WR
authors.lastname: English
authors.forename: Frédéric
authors.initials: F
authors.lastname: van den Brûle
authors.forename: Silvia
authors.initials: S
authors.lastname: Blacher
authors.forename: Christine
authors.initials: C
authors.lastname: Gilles
authors.forename: Carine
authors.initials: C
authors.lastname: Munaut
authors.forename: Erik
authors.initials: E
authors.lastname: Maquoi
authors.forename: Carlos
authors.initials: C
authors.lastname: Lopez-Otin
authors.forename: Gillian
authors.initials: G
authors.lastname: Murphy
authors.forename: Dylan R
authors.initials: DR
authors.lastname: Edwards
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Foidart
authors.forename: Agnès
authors.initials: A
authors.lastname: Noël
mesh_terms: D001943:Breast Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000201:enzymology / Q000556:secondary; D008207:Lymphatic Metastasis; D020782:Matrix Metalloproteinases / Q000096:biosynthesis* / Q000235:genetics; D053504:Matrix Metalloproteinases, Membrane-Associated; D009362:Neoplasm Metastasis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
chemical_list: D020782:Matrix Metalloproteinases; D053504:Matrix Metalloproteinases, Membrane-Associated