title: EMMPRIN-mediated MMP regulation in tumor and endothelial cells.
abstract: Tumor invasion and metastasis are multistep processes which require extracellular matrix remodeling by proteolytic enzymes such as matrix metalloproteinases (MMPs). The production of these enzymes is stimulated by many soluble or cell-bound factors. Among these factors, extracellular matrix metalloproteinase inducer (EMMPRIN) is known to increase in vitro stromal cell production of MMP-1, MMP-2 and MMP-3. In this study, we demonstrated that EMMPRIN-transfected MDA-MB-436 tumor cells displayed a more invasive capacity than vector-transfected cells in a modified Boyden chamber invasion assay. Using gelatin zymography and protein analyses, we showed that EMMPRIN-transfected cancer cells produced significantly more latent and active MMP-2 and MMP-3 than vector-transfected cancer cells. We found that EMMPRIN did not regulate MMP-1, MMP-9, membrane type-1 MMP (MT1-MMP) expression and had also no effect on the production of the specific tissue inhibitors of MMPs (TIMPs), TIMP-1 and TIMP-2. We also demonstrated that tumor-derived EMMPRIN stimulated MMP-1, -2, and -3 without modification of MMP-9, MT1-MMP, TIMP-1 and TIMP-2 production in human umbilical vein endothelial cells (HUVEC). These data provide support for the role of EMMPRIN in tumor invasion, metastasis, and neoangiogenesis by stimulating extracellular matrix remodeling around tumor cell clusters, stroma, and blood vessels.
authors.affiliation: Inserm U514, IFR53, CHU Maison-Blanche, Reims, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Caudroy
authors.forename: Myriam
authors.initials: M
authors.lastname: Polette
authors.forename: Béatrice
authors.initials: B
authors.lastname: Nawrocki-Raby
authors.forename: Jian
authors.initials: J
authors.lastname: Cao
authors.forename: Bryan P
authors.initials: BP
authors.lastname: Toole
authors.forename: Stanley
authors.initials: S
authors.lastname: Zucker
authors.forename: Philippe
authors.initials: P
authors.lastname: Birembaut
mesh_terms: D015703:Antigens, CD; D000951:Antigens, Neoplasm / Q000502:physiology; D051926:Basigin; D001943:Breast Neoplasms / Q000098:blood supply / Q000473:pathology*; D017077:Culture Media, Conditioned; D016895:Culture Media, Serum-Free; D018076:DNA, Complementary; D004730:Endothelium, Vascular / Q000201:enzymology*; D005780:Gelatin / Q000378:metabolism; D006801:Humans; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D015703:Antigens, CD; D000951:Antigens, Neoplasm; C497886:BSG protein, human; D017077:Culture Media, Conditioned; D016895:Culture Media, Serum-Free; D018076:DNA, Complementary; D008562:Membrane Glycoproteins; D011993:Recombinant Fusion Proteins; D051926:Basigin; D005780:Gelatin; D020782:Matrix Metalloproteinases