title: Induction of matrix metalloproteinase activation cascades based on membrane-type 1 matrix metalloproteinase: associated activation of gelatinase A, gelatinase B and collagenase 3.
abstract: SW1353 chondrosarcoma cells cultured in the presence of interleukin-1, concanavalin A or PMA secreted procollagenase 3 (matrix metalloproteinase-13). The enzyme was detected in the culture medium by Western blotting using a specific polyclonal antibody raised against recombinant human procollagenase 3. Oncostatin M enhanced the interleukin-1-induced production of procollagenase 3, whereas interleukin-4 decreased procollagenase 3 synthesis. The enzyme was latent except when the cells had been treated with concanavalin A, when a processed form of 48 kDa, which corresponds to the active form, was found in the culture medium and collagenolytic activity was detected by degradation of 14C-labelled type I collagen. The concanavalin A-induced activation of procollagenase 3 coincided with the processing of progelatinase A (matrix metalloproteinase-2) by the cells, as measured by gelatin zymography. In addition, progelatinase B (matrix metalloproteinase-9) was activated when gelatinase A and collagenase 3 were in their active forms. Concanavalin A treatment of SW1353 cells increased the amount of membrane-type-1 matrix metalloproteinase protein in the cell membranes, suggesting that this membrane-bound enzyme participates in an activation cascade involving collagenase 3 and the gelatinases. This cascade was effectively inhibited by tissue inhibitors of metalloproteinases-2 and -3. Tissue inhibitor of metalloproteinases-1, which is a much weaker inhibitor of membrane-type 1 matrix metalloproteinase than tissue inhibitors of metalloproteinases-2 and -3 [Will, Atkinson, Butler, Smith and Murphy (1996) J. Biol. Chem. 271, 17119-17123], was a weaker inhibitor of the activation cascade.
authors.affiliation: Department of Cell and Molecular Biology, Strangeways Research Laboratory, Worts' Causeway, Cambridge, CB1 4RN, U.K.
authors.forename: S
authors.initials: S
authors.lastname: Cowell
authors.forename: V
authors.initials: V
authors.lastname: Knäuper
authors.forename: M L
authors.initials: ML
authors.lastname: Stewart
authors.forename: M P
authors.initials: MP
authors.lastname: D'Ortho
authors.forename: H
authors.initials: H
authors.lastname: Stanton
authors.forename: R M
authors.initials: RM
authors.lastname: Hembry
authors.forename: C
authors.initials: C
authors.lastname: López-Otín
authors.forename: J J
authors.initials: JJ
authors.lastname: Reynolds
authors.forename: G
authors.initials: G
authors.lastname: Murphy
mesh_terms: D015153:Blotting, Western; D002462:Cell Membrane / Q000201:enzymology; D002813:Chondrosarcoma / Q000201:enzymology; D017364:Collagenases / Q000096:biosynthesis / Q000378:metabolism*; D003208:Concanavalin A / Q000494:pharmacology; D017077:Culture Media, Conditioned; D004789:Enzyme Activation; D004790:Enzyme Induction / Q000187:drug effects; D005341:Fibrinolysin / Q000502:physiology; D018093:Gelatinases / Q000378:metabolism*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D053509:Matrix Metalloproteinase 13; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D008666:Metalloendopeptidases / Q000378:metabolism*; D011480:Protease Inhibitors / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism / Q000494:pharmacology; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism / Q000494:pharmacology; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D017077:Culture Media, Conditioned; D007375:Interleukin-1; D011480:Protease Inhibitors; D019715:Tissue Inhibitor of Metalloproteinase-1; D019717:Tissue Inhibitor of Metalloproteinase-3; D003208:Concanavalin A; D019716:Tissue Inhibitor of Metalloproteinase-2; D005341:Fibrinolysin; D017364:Collagenases; D018093:Gelatinases; C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D013755:Tetradecanoylphorbol Acetate