Membrane-type 4 matrix metalloproteinase promotes breast cancer growth and metastases

Chabottaux, Vincent, Sounni, Nor Eddine, Pennington, Caroline J, English, William R ORCID: https://orcid.org/0000-0003-3024-2441, van den Brûle, Frédéric, Blacher, Silvia, Gilles, Christine, Munaut, Carine, Maquoi, Erik, Lopez-Otin, Carlos, Murphy, Gillian, Edwards, Dylan ORCID: https://orcid.org/0000-0002-3292-2064, Foidart, Jean-Michel and Noel, Agnès (2006) Membrane-type 4 matrix metalloproteinase promotes breast cancer growth and metastases. Cancer Research, 66 (10). pp. 5165-5172.

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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. (Cancer Res 2006; 66(10): 5165-72)

Item Type:	Article
Uncontrolled Keywords:	sdg 3 - good health and well-being ,/dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being
Faculty \ School:	Faculty of Science > School of Biological Sciences Faculty of Medicine and Health Sciences > Norwich Medical School
UEA Research Groups:	Faculty of Medicine and Health Sciences > Research Centres > Norwich Institute for Healthy Aging Faculty of Medicine and Health Sciences > Research Groups > Cancer Studies Faculty of Medicine and Health Sciences > Research Centres > Metabolic Health
Depositing User:	EPrints Services
Date Deposited:	01 Oct 2010 13:38
Last Modified:	24 Sep 2024 09:47
URI:	https://ueaeprints.uea.ac.uk/id/eprint/1182
DOI:	10.1158/0008-5472.CAN-05-3012

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