Membrane-type 4 matrix metalloproteinase (MT4-MMP) induces lung metastasis by alteration of primary breast tumour vascular architecture
Vincent Chabottaux
Laboratory of Tumor and Developmental Biology, Groupe Interdisciplinaire de Génoprotéomique Appliquée-Cancer (GIGA-Cancer), University of Liege, Tour de Pathologie, Liège, Belgium
Search for more papers by this authorStéphanie Ricaud
CEA, DSV, Institut d’Imagerie Biomédicale (I 2 BM), Service Hospitalier Frédéric Joliot, Laboratoire d’Imagerie Moléculaire Expérimentale, Orsay Cedex, France
INSERM U803, 4 place du général Leclerc, Orsay Cedex, France
Search for more papers by this authorLaurent Host
Laboratory of Tumor and Developmental Biology, Groupe Interdisciplinaire de Génoprotéomique Appliquée-Cancer (GIGA-Cancer), University of Liege, Tour de Pathologie, Liège, Belgium
Search for more papers by this authorSilvia Blacher
Laboratory of Tumor and Developmental Biology, Groupe Interdisciplinaire de Génoprotéomique Appliquée-Cancer (GIGA-Cancer), University of Liege, Tour de Pathologie, Liège, Belgium
Search for more papers by this authorAlexandra Paye
Laboratory of Tumor and Developmental Biology, Groupe Interdisciplinaire de Génoprotéomique Appliquée-Cancer (GIGA-Cancer), University of Liege, Tour de Pathologie, Liège, Belgium
Search for more papers by this authorMarc Thiry
Laboratory of Cell and Tissue Biology, University of Liège, Liège, Belgium
Search for more papers by this authorAnikitos Garofalakis
CEA, DSV, Institut d’Imagerie Biomédicale (I 2 BM), Service Hospitalier Frédéric Joliot, Laboratoire d’Imagerie Moléculaire Expérimentale, Orsay Cedex, France
INSERM U803, 4 place du général Leclerc, Orsay Cedex, France
Search for more papers by this authorCarine Pestourie
CEA, DSV, Institut d’Imagerie Biomédicale (I 2 BM), Service Hospitalier Frédéric Joliot, Laboratoire d’Imagerie Moléculaire Expérimentale, Orsay Cedex, France
INSERM U803, 4 place du général Leclerc, Orsay Cedex, France
Search for more papers by this authorKarine Gombert
CEA, DSV, Institut d’Imagerie Biomédicale (I 2 BM), Service Hospitalier Frédéric Joliot, Laboratoire d’Imagerie Moléculaire Expérimentale, Orsay Cedex, France
INSERM U803, 4 place du général Leclerc, Orsay Cedex, France
Search for more papers by this authorFrançoise Bruyere
Laboratory of Tumor and Developmental Biology, Groupe Interdisciplinaire de Génoprotéomique Appliquée-Cancer (GIGA-Cancer), University of Liege, Tour de Pathologie, Liège, Belgium
Search for more papers by this authorDaniel Lewandowsky
CEA, DSV, Institut de Radiobiologie Cellulaire et Moléculaire (iRCM), Laboratoire de recherche sur la Réparation et la Transcription dans les cellules Souches (LRTS), Fontenay-aux-Roses cedex, France
Search for more papers by this authorBertrand Tavitian
CEA, DSV, Institut d’Imagerie Biomédicale (I 2 BM), Service Hospitalier Frédéric Joliot, Laboratoire d’Imagerie Moléculaire Expérimentale, Orsay Cedex, France
INSERM U803, 4 place du général Leclerc, Orsay Cedex, France
Search for more papers by this authorJean-Michel Foidart
Laboratory of Tumor and Developmental Biology, Groupe Interdisciplinaire de Génoprotéomique Appliquée-Cancer (GIGA-Cancer), University of Liege, Tour de Pathologie, Liège, Belgium
Centre Hospitalier Universitaire (CHU), Hopital de la Citadelle, Liège, Belgium
Search for more papers by this authorFrédéric Duconge
CEA, DSV, Institut d’Imagerie Biomédicale (I 2 BM), Service Hospitalier Frédéric Joliot, Laboratoire d’Imagerie Moléculaire Expérimentale, Orsay Cedex, France
INSERM U803, 4 place du général Leclerc, Orsay Cedex, France
Search for more papers by this authorCorresponding Author
Agnès Noel
Laboratory of Tumor and Developmental Biology, Groupe Interdisciplinaire de Génoprotéomique Appliquée-Cancer (GIGA-Cancer), University of Liege, Tour de Pathologie, Liège, Belgium
Correspondence to: A. NOEL, Laboratory of Tumor and Developmental Biology, University of Liège, Tour de Pathologie (B23), Sart-Tilman, B-4000 Liège, Belgium.Tel.: +32-4-366 25.69Fax: +32-4-366 29 36E-mail: [email protected]Search for more papers by this authorVincent Chabottaux
Laboratory of Tumor and Developmental Biology, Groupe Interdisciplinaire de Génoprotéomique Appliquée-Cancer (GIGA-Cancer), University of Liege, Tour de Pathologie, Liège, Belgium
Search for more papers by this authorStéphanie Ricaud
CEA, DSV, Institut d’Imagerie Biomédicale (I 2 BM), Service Hospitalier Frédéric Joliot, Laboratoire d’Imagerie Moléculaire Expérimentale, Orsay Cedex, France
INSERM U803, 4 place du général Leclerc, Orsay Cedex, France
Search for more papers by this authorLaurent Host
Laboratory of Tumor and Developmental Biology, Groupe Interdisciplinaire de Génoprotéomique Appliquée-Cancer (GIGA-Cancer), University of Liege, Tour de Pathologie, Liège, Belgium
Search for more papers by this authorSilvia Blacher
Laboratory of Tumor and Developmental Biology, Groupe Interdisciplinaire de Génoprotéomique Appliquée-Cancer (GIGA-Cancer), University of Liege, Tour de Pathologie, Liège, Belgium
Search for more papers by this authorAlexandra Paye
Laboratory of Tumor and Developmental Biology, Groupe Interdisciplinaire de Génoprotéomique Appliquée-Cancer (GIGA-Cancer), University of Liege, Tour de Pathologie, Liège, Belgium
Search for more papers by this authorMarc Thiry
Laboratory of Cell and Tissue Biology, University of Liège, Liège, Belgium
Search for more papers by this authorAnikitos Garofalakis
CEA, DSV, Institut d’Imagerie Biomédicale (I 2 BM), Service Hospitalier Frédéric Joliot, Laboratoire d’Imagerie Moléculaire Expérimentale, Orsay Cedex, France
INSERM U803, 4 place du général Leclerc, Orsay Cedex, France
Search for more papers by this authorCarine Pestourie
CEA, DSV, Institut d’Imagerie Biomédicale (I 2 BM), Service Hospitalier Frédéric Joliot, Laboratoire d’Imagerie Moléculaire Expérimentale, Orsay Cedex, France
INSERM U803, 4 place du général Leclerc, Orsay Cedex, France
Search for more papers by this authorKarine Gombert
CEA, DSV, Institut d’Imagerie Biomédicale (I 2 BM), Service Hospitalier Frédéric Joliot, Laboratoire d’Imagerie Moléculaire Expérimentale, Orsay Cedex, France
INSERM U803, 4 place du général Leclerc, Orsay Cedex, France
Search for more papers by this authorFrançoise Bruyere
Laboratory of Tumor and Developmental Biology, Groupe Interdisciplinaire de Génoprotéomique Appliquée-Cancer (GIGA-Cancer), University of Liege, Tour de Pathologie, Liège, Belgium
Search for more papers by this authorDaniel Lewandowsky
CEA, DSV, Institut de Radiobiologie Cellulaire et Moléculaire (iRCM), Laboratoire de recherche sur la Réparation et la Transcription dans les cellules Souches (LRTS), Fontenay-aux-Roses cedex, France
Search for more papers by this authorBertrand Tavitian
CEA, DSV, Institut d’Imagerie Biomédicale (I 2 BM), Service Hospitalier Frédéric Joliot, Laboratoire d’Imagerie Moléculaire Expérimentale, Orsay Cedex, France
INSERM U803, 4 place du général Leclerc, Orsay Cedex, France
Search for more papers by this authorJean-Michel Foidart
Laboratory of Tumor and Developmental Biology, Groupe Interdisciplinaire de Génoprotéomique Appliquée-Cancer (GIGA-Cancer), University of Liege, Tour de Pathologie, Liège, Belgium
Centre Hospitalier Universitaire (CHU), Hopital de la Citadelle, Liège, Belgium
Search for more papers by this authorFrédéric Duconge
CEA, DSV, Institut d’Imagerie Biomédicale (I 2 BM), Service Hospitalier Frédéric Joliot, Laboratoire d’Imagerie Moléculaire Expérimentale, Orsay Cedex, France
INSERM U803, 4 place du général Leclerc, Orsay Cedex, France
Search for more papers by this authorCorresponding Author
Agnès Noel
Laboratory of Tumor and Developmental Biology, Groupe Interdisciplinaire de Génoprotéomique Appliquée-Cancer (GIGA-Cancer), University of Liege, Tour de Pathologie, Liège, Belgium
Correspondence to: A. NOEL, Laboratory of Tumor and Developmental Biology, University of Liège, Tour de Pathologie (B23), Sart-Tilman, B-4000 Liège, Belgium.Tel.: +32-4-366 25.69Fax: +32-4-366 29 36E-mail: [email protected]Search for more papers by this authorAbstract
The present study aims at investigating the mechanism by which membrane-type 4 matrix metalloproteinase (MT4-MMP), a membrane-anchored MMP expressed by human breast tumour cells promotes the metastatic dissemination into lung. We applied experimental (intravenous) and spontaneous (subcutaneous) models of lung metastasis using human breast adenocarcinoma MDA-MB-231 cells overexpressing or not MT4-MMP. We found that MT4-MMP does not affect lymph node colonization nor extravasation of cells from the bloodstream, but increases the intravasation step leading to metastasis. Ultrastructural and fluorescent microscopic observations coupled with automatic computer-assisted quantifications revealed that MT4-MMP expression induces blood vessel enlargement and promotes the detachment of mural cells from the vascular tree, thus causing an increased tumour vascular leak. On this basis, we propose that MT4-MMP promotes lung metastasis by disturbing the tumour vessel integrity and thereby facilitating tumour cell intravasation.
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