1. Down-Regulation of MT1-MMP Expression by the α3 Chain of Type IV Collagen Inhibits Bronchial Tumor Cell Line Invasion
- Author
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Agnès Noël, Jean-Claude Monboisse, Jean-Michel Foidart, Alain Colige, Pierre Dehan, Laurette Volders, Myriam Polette, Christine Gilles, Corinne Martinella-Catusse, Philippe Birembaut, Carine Munaut, Dynamique cellulaire et moléculaire de la muqueuse respiratoire, Université de Reims Champagne-Ardenne (URCA)-IFR53-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratory of Tumor and Developmental Biology, Université de Liège-CHU Sart-Tilman, Biomolécules : interactions moléculaires, cellulaires et cellules-matrice extracellulaire (BIMCCME), Université de Reims Champagne-Ardenne (URCA)-Centre Hospitalier Universitaire de Reims (CHU Reims)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'histologie, cytologie, biologie cellulaire et moléculaire Pol Bouin, Université de Reims Champagne-Ardenne (URCA)-Centre Hospitalier Universitaire de Reims (CHU Reims), and Birembaut, Philippe
- Subjects
Pathology ,Lung Neoplasms ,Transcription, Genetic ,Matrix metalloproteinase ,[SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract ,Type IV collagen ,MESH: Collagen ,Cell Line, Transformed ,Metalloproteinase ,Reverse Transcriptase Polymerase Chain Reaction ,MESH: Gene Expression Regulation, Enzymologic ,MESH: Bronchi ,Metalloendopeptidases ,Recombinant Proteins ,Cell Transformation, Neoplastic ,medicine.anatomical_structure ,Matrix Metalloproteinase 2 ,Collagen ,medicine.medical_specialty ,Matrix Metalloproteinases, Membrane-Associated ,Bronchi ,macromolecular substances ,Respiratory Mucosa ,Biology ,Gene Expression Regulation, Enzymologic ,Article ,Cell Line ,Pathology and Forensic Medicine ,Gentamicin protection assay ,medicine ,Humans ,Neoplasm Invasiveness ,MESH: Matrix Metalloproteinases, Membrane-Associated ,MESH: Cell Line, Transformed ,Molecular Biology ,Basement membrane ,Tissue Inhibitor of Metalloproteinase-2 ,MESH: Humans ,Cell Biology ,Molecular biology ,Peptide Fragments ,Epithelium ,MESH: Cell Line ,MESH: Lung Neoplasms ,MESH: Matrix Metalloproteinase 2 ,MESH: Genes, ras ,Genes, ras ,MESH: Cell Transformation, Neoplastic ,Tumor progression ,Cell culture ,MESH: Metalloendopept ,[SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract - Abstract
International audience; The basement membrane (BM) is the first barrier encountered by tumor cells when they become invasive. Moreover, some invasive tumor clusters are surrounded by a remnant or neosynthetized BM material. We have previously reported the presence of a particular alpha chain of type IV collagen, the alpha3(IV) chain, in bronchopulmonary carcinomas. This chain was not detected in the normal bronchial epithelium, but was found around some invasive tumor cluster BM. In the present study, we examined the effects of the alpha3(IV) chain on the invasive properties of bronchial tumor cell lines, with special emphasis on their expression of matrix metalloproteinase-2 (MMP-2) and its activator, membrane type 1-matrix metalloproteinase (MT1-MMP), which is largely involved in tumor progression. Two epithelial bronchial cell lines (16HBE14o- and BZR), showing different invasive abilities, were evaluated. Using the Boyden chamber invasion assay, we demonstrated that the alpha3(IV) chain inhibits the invasive properties of BZR cells and modifies their morphology by inducing an epithelial cell shape. In the presence of the recombinant NC1 domain of the alpha3(IV) chain, the expression of MMP-2 and tissue inhibitor of metalloproteinase-2 (TIMP-2) was not modified in either cell line. The NC1 alpha3(IV) domain did not modulate the MT1-MMP expression of noninvasive 16HBE14o- cells, whereas a 50% decrease of MT1-MMP mRNA was observed in invasive BZR cells. Accordingly, Western blot analyses showed a disappearance of the 45-kd MT1-MMP form when BZR cells were treated with the recombinant NC1 alpha3(IV) domain. These findings suggest that the alpha3 chain of type IV collagen may play a role in tumor invasion, at least by decreasing the expression and synthesis of MT1-MMP.
- Published
- 2001
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