QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

This Article Figures Only Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gilles, C. Articles by Foidart, J.-M. Search for Related Content PubMed PubMed Citation Articles by Gilles, C. Articles by Foidart, J.-M. Social Bookmarking                         What's this?

Contribution of MT1-MMP and of human laminin-5 2 chain degradation to mammary epithelial cell migration

Christine Gilles^1,*,, Myriam Polette^2,*, Christelle Coraux², Jean-Marie Tournier², Guerrino Meneguzzi³, Carine Munaut¹, Laure Volders¹, Patricia Rousselle⁴, Philippe Birembaut² and Jean-Michel Foidart¹

¹ Laboratory of Tumor and Developmental Biology, University of Liège, C.H.U. Sart-Tilman, B23, Liège, Belgium
² Unité INSERM U.514, Laboratoire Pol Bouin, IFR 53, C.H.U. Maison Blanche, Reims, France
³ Unité INSERM U.385, Faculty of Medicine, Nice, France
⁴ Institut de Biologie et de Chimie des Protéines, CNRS, U.P.R. 412, Lyon, France
^* These authors contributed equally to this research
Author for correspondence (e-mail: cgilles{at}ulg.ac.be )

Accepted May 9, 2001

Membrane-type matrix metalloproteinase 1 (MT1-MMP) is a membrane-anchored matrix metalloproteinase (MMP) that is frequently associated with processes involving tissue remodelling and cell migration. We have examined MT1-MMP expression and subcellular distribution as a function of MCF10A mammary epithelial cell migration using an in vitro outgrowth migration assay. Stronger expression of MT1-MMP was observed at the mRNA and at the protein level in cells at the periphery of the outgrowth. As shown by videomicroscopy, these cells were involved in an orientated cell migration, in contrast to stationary cells distant from the periphery. Furthermore, MT1-MMP was mainly distributed in lamellipodia of migratory cells, as well as at their basal surface in contact with the substrate. Laminin-5 (Ln-5), a recently described substrate for MT1-MMP, was deposited preferentially in the matrix by migratory cells. Fragments of the 2 subunit of Ln-5 were also identified in migratory cultures of MCF10A cells, attesting to its proteolytic degradation. These fragments corresponded in size to those we observed after incubation of purified human Ln-5 with the recombinant catalytic domain of human MT1-MMP. We also show that anti-Ln5 blocking antibodies, MMP inhibitors (BB94 and TIMP-2) and MT1-MMP antisense oligonucleotides significantly decreased MCF10A cell migration. Taken together, these observations demonstrate that MT1-MMP is spatially and temporally regulated during MCF10A cell migration, and suggest that MT1-MMP-mediated pericellular proteolysis of Ln-5 2 chain could contribute to this process.

Key words: MT1-MMP, Laminin-5, Migration, MCF10A, Epithelial cells

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				N. Koshikawa, T. Minegishi, A. Sharabi, V. Quaranta, and M. Seiki Membrane-type Matrix Metalloproteinase-1 (MT1-MMP) Is a Processing Enzyme for Human Laminin {gamma}2 Chain J. Biol. Chem., January 7, 2005; 280(1): 88 - 93. [Abstract] [Full Text] [PDF]

				Y.-A. Choi, H.-K. Lim, J.-R. Kim, C.-H. Lee, Y.-J. Kim, S.-S. Kang, and S.-H. Baek Group IB Secretory Phospholipase A2 Promotes Matrix Metalloproteinase-2-mediated Cell Migration via the Phosphatidylinositol 3-Kinase and Akt Pathway J. Biol. Chem., August 27, 2004; 279(35): 36579 - 36585. [Abstract] [Full Text] [PDF]

				M. Katayama, N. Sanzen, A. Funakoshi, and K. Sekiguchi Laminin {gamma}2-Chain Fragment in the Circulation: A Prognostic Indicator of Epithelial Tumor Invasion Cancer Res., January 1, 2003; 63(1): 222 - 229. [Abstract] [Full Text] [PDF]