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J. Cell Biol., Volume 146, Number 2, July 26, 1999 517-529
Copyright © 1999 by The Rockefeller University Press.

Airway Epithelial Cell Migration Dynamics: MMP-9 Role in Cell–Extracellular Matrix Remodeling

Claire Legranda, Christine Gillesc, Jean-Marie Zahma, Myriam Polettea,b, Anne-Cécile Buissona, Hervé Kaplana, Philippe Birembauta,b, and Jean-Marie Tourniera
a INSERM Unité 514, IFR 53, Université de Reims,
b Laboratoire Pol Bouin, Unité de Biologie Cellulaire, Centre Hospitalier Universitaire Maison Blanche, 51092 Reims, France
c Laboratory of Tumor and Developmental Biology, University of Liège, C.H.U. Sart-Tilman, B23, 4000 Liège, Belgium

Correspondence to: Jean-Marie Tournier, INSERM Unité 514, Centre Hospitalier Universitaire Maison Blanche, 45 rue Cognacq-Jay, 51092 Reims Cedex, France., jm.tournier{at}univ-reims.fr (E-mail), 33-3-26-78-77-70 (phone), 33-3-26-06-58-61 (fax)

Cell spreading and migration associated with the expression of the 92-kD gelatinase (matrix metalloproteinase 9 or MMP-9) are important mechanisms involved in the repair of the respiratory epithelium. We investigated the location of MMP-9 and its potential role in migrating human bronchial epithelial cells (HBEC). In vivo and in vitro, MMP-9 accumulated in migrating HBEC located at the leading edge of a wound and MMP-9 expression paralleled cell migration speed. MMP-9 accumulated through an actin-dependent pathway in the advancing lamellipodia of migrating cells and was subsequently found active in the extracellular matrix (ECM). Lamellipodia became anchored through primordial contacts established with type IV collagen. MMP-9 became amassed behind collagen IV where there were fewer cell–ECM contacts. Both collagen IV and MMP-9 were involved in cell migration because when cell–collagen IV interaction was blocked, cells spread slightly but did not migrate; and when MMP-9 activation was prevented, cells remained fixed on primordial contacts and did not advance at all. These observations suggest that MMP-9 controls the migration of repairing HBEC by remodeling the provisional ECM implicated in primordial contacts.

Key Words: cell migration, gelatinase, matrix metalloproteinase, bronchial epithelium, wound repair


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