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: Vincent Chabottaux, Nor Eddine Sounni, Caroline J Pennington, William R English, Frédéric van den Brûle, Silvia Blacher, Christine Gilles, Carine Munaut, Erik Maquoi, Carlos Lopez-Otin, Gillian Murphy, Dylan R Edwards, Jean-Michel Foidart, Agnès Noël
• Journal: Cancer research (Cancer Res) Vol. 66 Issue 10 Pg. 5165-72 (May 15 2006) ISSN: 0008-5472 [Print] United States
• PMID: 16707440 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Matrix Metalloproteinases
• Matrix Metalloproteinases, Membrane-Associated

Topics

• Breast Neoplasms (enzymology, genetics, pathology)
• Cell Growth Processes (physiology)
• Cell Line, Tumor
• Humans
• Immunohistochemistry
• Lung Neoplasms (enzymology, secondary)
• Lymphatic Metastasis
• Matrix Metalloproteinases (biosynthesis, genetics)
• Matrix Metalloproteinases, Membrane-Associated
• Neoplasm Metastasis
• Reverse Transcriptase Polymerase Chain Reaction
• Transfection