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PMID: 9171346 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Control of type IV collagenase activity by components of the urokinase-plasmin system: a regulatory mechanism with cell-bound reactants.

The EMBO journal ·Vol. 16 ·No. 9 ·1997-05-01 ·Pages 2319-32

Mazzieri R, Masiero L, Zanetta L, Monea S, Onisto M, Garbisa S, Mignatti P

Abstract

The urokinase-type plasminogen activator (uPA) and the matrix-degrading metalloproteinases MMP-2 and MMP-9 (type IV collagenases/gelatinases) have been implicated in a variety of invasive processes, including tumor invasion, metastasis and angiogenesis. MMP-2 and MMP-9 are secreted in the form of inactive zymogens that are activated extracellularly, a fundamental process for the control of their activity. The physiological mechanism(s) of gelatinase activation are still poorly understood; their comprehension may provide tools to control cell invasion. The data reported in this paper show multiple roles of the uPA-plasmin system in the control of gelatinase activity: (i) both gelatinases are associated with the cell surface; binding of uPA and plasmin(ogen) to the cell surface results in gelatinase activation without the action of other metallo- or acid proteinases; (ii) inhibition of uPA or plasminogen binding to the cell surface blocks gelatinase activation; (iii) in soluble phase plasmin degrades both gelatinases; and (iv) gelatinase activation and degradation occur in a dose- and time-dependent manner in the presence of physiological plasminogen and uPA concentrations. Thus, the uPA-plasmin system may represent a physiological mechanism for the control of gelatinase activity.

MeSH Terms
Collagenases/metabolism Enzyme Activation Enzyme Precursors/metabolism Fibrinolysin/metabolism Gelatinases/metabolism Humans Matrix Metalloproteinase 2 Matrix Metalloproteinase 9 Metalloendopeptidases/metabolism Molecular Weight Plasminogen Activators/metabolism Receptors, Cell Surface/metabolism Receptors, Urokinase Plasminogen Activator Surface Properties Tumor Cells, Cultured Urokinase-Type Plasminogen Activator/metabolism
Chemicals
Enzyme Precursors PLAUR protein, human Receptors, Cell Surface Receptors, Urokinase Plasminogen Activator Plasminogen Activators Fibrinolysin Urokinase-Type Plasminogen Activator Collagenases Gelatinases Metalloendopeptidases progelatinase Matrix Metalloproteinase 2 Matrix Metalloproteinase 9
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Mazzieri R
Dipartimento di Genetica e Microbiologia, Università di Pavia, Italy.
Masiero L
Zanetta L
Monea S
Onisto M
Garbisa S
Mignatti P
References (59)
59 references, click to expand
  1. Mouse L cells expressing human prourokinase-type plasminogen activator: effects on extracellular matrix degradation and invasion.
    J Cell Biol. 1989 Aug;109(2):915-25 PMID: 2503527
  2. SV40-transformed human lung fibroblasts secrete a 92-kDa type IV collagenase which is identical to that secreted by normal human macrophages.
    J Biol Chem. 1989 Oct 15;264(29):17213-21 PMID: 2551898
  3. Human 72-kilodalton type IV collagenase forms a complex with a tissue inhibitor of metalloproteases designated TIMP-2.
    Proc Natl Acad Sci U S A. 1989 Nov;86(21):8207-11 PMID: 2554304
  4. Cloning and expression of the receptor for human urokinase plasminogen activator, a central molecule in cell surface, plasmin dependent proteolysis.
    EMBO J. 1990 Feb;9(2):467-74 PMID: 1689240
  5. Development of a novel substrate capture immunoassay for the detection of a neutral metalloproteinase capable of degrading basement membrane (type IV) collagen.
    J Immunol Methods. 1990 Feb 9;126(2):239-45 PMID: 2154522
  6. The human receptor for urokinase plasminogen activator. NH2-terminal amino acid sequence and glycosylation variants.
    J Biol Chem. 1990 Apr 15;265(11):6453-60 PMID: 2156852
  7. Tissue inhibitor of metalloproteinases-2 inhibits the activation of 72 kDa progelatinase by fibroblast membranes.
    Biochim Biophys Acta. 1991 Aug 30;1079(2):242-6 PMID: 1911847
  8. Substrate specificities and activation mechanisms of matrix metalloproteinases.
    Biochem Soc Trans. 1991 Aug;19(3):715-8 PMID: 1783204
  9. Interaction of 92-kDa type IV collagenase with the tissue inhibitor of metalloproteinases prevents dimerization, complex formation with interstitial collagenase, and activation of the proenzyme with stromelysin.
    J Biol Chem. 1992 Mar 5;267(7):4583-91 PMID: 1311314
  10. Molecular cloning, chromosomal localization, and bacterial expression of a murine macrophage metalloelastase.
    J Biol Chem. 1992 Mar 5;267(7):4664-71 PMID: 1537850
  11. The C-terminal domain of 72 kDa gelatinase A is not required for catalysis, but is essential for membrane activation and modulates interactions with tissue inhibitors of metalloproteinases.
    Biochem J. 1992 May 1;283 ( Pt 3):637-41 PMID: 1317162
  12. Correlation of serum metalloproteinase levels with lung cancer metastasis and response to therapy.
    Cancer Res. 1992 Aug 15;52(16):4548-9 PMID: 1322794
  13. Tumor cell surface-associated binding site for the M(r) 72,000 type IV collagenase.
    Cancer Res. 1992 Oct 15;52(20):5845-8 PMID: 1394213
  14. Proteolytic processing of the 72,000-Da type IV collagenase by urokinase plasminogen activator.
    Exp Cell Res. 1992 Oct;202(2):471-6 PMID: 1397099
  15. Cell-mediated degradation of type IV collagen and gelatin films is dependent on the activation of matrix metalloproteinases.
    Biochem J. 1992 Dec 1;288 ( Pt 2):605-11 PMID: 1463464
  16. Activation mechanisms of the precursors of matrix metalloproteinases 1, 2 and 3.
    Matrix Suppl. 1992;1:237-44 PMID: 1480033
  17. Biology and biochemistry of proteinases in tumor invasion.
    Physiol Rev. 1993 Jan;73(1):161-95 PMID: 8419965
  18. Plasma membrane-dependent activation of the 72-kDa type IV collagenase is prevented by complex formation with TIMP-2.
    J Biol Chem. 1993 Jul 5;268(19):14033-9 PMID: 8314771
  19. Binding and localization of M(r) 72,000 matrix metalloproteinase at cell surface invadopodia.
    Cancer Res. 1993 Jul 1;53(13):3159-64 PMID: 8391388
  20. The role of plasminogen activators in the regulation of connective tissue metalloproteinases.
    Ann N Y Acad Sci. 1992 Dec 4;667:1-12 PMID: 1339240
  21. Competition between plasminogen and tissue plasminogen activator for cellular binding sites.
    Blood. 1993 Oct 15;82(8):2433-41 PMID: 8400293
  22. Structural biochemistry and activation of matrix metalloproteases.
    Curr Opin Cell Biol. 1993 Oct;5(5):891-7 PMID: 8240832
  23. Activation of the 92 kDa type IV collagenase by tissue kallikrein.
    J Cell Physiol. 1993 Dec;157(3):587-93 PMID: 8253870
  24. Tumor cell interactions with the extracellular matrix during invasion and metastasis.
    Annu Rev Cell Biol. 1993;9:541-73 PMID: 8280471
  25. Direct evidence linking expression of matrix metalloproteinase 9 (92-kDa gelatinase/collagenase) to the metastatic phenotype in transformed rat embryo cells.
    Proc Natl Acad Sci U S A. 1994 May 10;91(10):4293-7 PMID: 8183903
  26. A matrix metalloproteinase expressed on the surface of invasive tumour cells.
    Nature. 1994 Jul 7;370(6484):61-5 PMID: 8015608
  27. The C-terminal region of membrane type matrix metalloproteinase is a functional transmembrane domain required for pro-gelatinase A activation.
    J Biol Chem. 1995 Jan 13;270(2):801-5 PMID: 7822314
  28. Matrix metalloproteinase-2 is an interstitial collagenase. Inhibitor-free enzyme catalyzes the cleavage of collagen fibrils and soluble native type I collagen generating the specific 3/4- and 1/4-length fragments.
    J Biol Chem. 1995 Mar 17;270(11):5872-6 PMID: 7890717
  29. Membrane-type matrix metalloproteinase (MT-MMP) gene is expressed in stromal cells of human colon, breast, and head and neck carcinomas.
    Proc Natl Acad Sci U S A. 1995 Mar 28;92(7):2730-4 PMID: 7708715
  30. Molecular insights into cancer invasion: strategies for prevention and intervention.
    Cancer Res. 1995 May 1;55(9):1856-62 PMID: 7728753
  31. Steps involved in activation of the complex of pro-matrix metalloproteinase 2 (progelatinase A) and tissue inhibitor of metalloproteinases (TIMP)-2 by 4-aminophenylmercuric acetate.
    Biochem J. 1995 Jun 1;308 ( Pt 2):645-51 PMID: 7772054
  32. ECM degradation by cultured human mesangial cells is mediated by a PA/plasmin/MMP-2 cascade.
    Kidney Int. 1995 Apr;47(4):1039-47 PMID: 7540230
  33. The cell biology of the plasminogen system.
    FASEB J. 1995 Jul;9(10):939-45 PMID: 7615163
  34. Tumor and stromal expression of matrix metalloproteinases and their role in tumor progression.
    Invasion Metastasis. 1994-1995;14(1-6):234-45 PMID: 7657516
  35. Metalloproteinases in tumor progression: the contribution of MMP-9.
    Invasion Metastasis. 1994-1995;14(1-6):246-58 PMID: 7657517
  36. Progelatinase A activation during tumor cell invasion.
    Invasion Metastasis. 1994-1995;14(1-6):259-68 PMID: 7657518
  37. Localization of matrix metalloproteinase MMP-2 to the surface of invasive cells by interaction with integrin alpha v beta 3.
    Cell. 1996 May 31;85(5):683-93 PMID: 8646777
  38. Endogenous activation of latent collagenase by rheumatoid synovial cells. Evidence for a role of plasminogen activator.
    N Engl J Med. 1977 May 5;296(18):1017-23 PMID: 66627
  39. Electrophoretic analysis of plasminogen activators in polyacrylamide gels containing sodium dodecyl sulfate and copolymerized substrates.
    Anal Biochem. 1980 Feb;102(1):196-202 PMID: 7188842
  40. Quantitation of basement membrane collagen degradation by living tumor cells in vitro.
    Cancer Lett. 1980 Jun;9(4):359-66 PMID: 7397689
  41. Plasminogen is present in the basal layer of the epidermis.
    J Invest Dermatol. 1983 Apr;80(4):297-9 PMID: 6339645
  42. A cellular binding site for the Mr 55,000 form of the human plasminogen activator, urokinase.
    J Cell Biol. 1985 Jan;100(1):86-92 PMID: 3880760
  43. Differentiation-enhanced binding of the amino-terminal fragment of human urokinase plasminogen activator to a specific receptor on U937 monocytes.
    Proc Natl Acad Sci U S A. 1985 Aug;82(15):4939-43 PMID: 2991901
  44. Autocrine saturation of pro-urokinase receptors on human A431 cells.
    Cell. 1986 Jun 6;45(5):675-84 PMID: 3011276
  45. Binding of plasminogen to cultured human endothelial cells.
    J Biol Chem. 1986 Sep 5;261(25):11656-62 PMID: 3745161
  46. Tumor invasion through the human amniotic membrane: requirement for a proteinase cascade.
    Cell. 1986 Nov 21;47(4):487-98 PMID: 3022933
  47. The plasminogen system and cell surfaces: evidence for plasminogen and urokinase receptors on the same cell type.
    J Cell Biol. 1986 Dec;103(6 Pt 1):2411-20 PMID: 3023400
  48. The receptor-binding sequence of urokinase. A biological function for the growth-factor module of proteases.
    J Biol Chem. 1987 Apr 5;262(10):4437-40 PMID: 3031025
  49. H-ras oncogene-transformed human bronchial epithelial cells (TBE-1) secrete a single metalloprotease capable of degrading basement membrane collagen.
    J Biol Chem. 1988 May 15;263(14):6579-87 PMID: 2834383
  50. Membrane and matrix localization of proteinases: a common theme in tumor cell invasion and angiogenesis.
    Biochim Biophys Acta. 1988 Aug 3;948(1):67-85 PMID: 2456098
  51. Cell-associated plasminogen activation: regulation and physiological functions.
    Annu Rev Cell Biol. 1988;4:93-126 PMID: 3143380
  52. The activation of human type IV collagenase proenzyme. Sequence identification of the major conversion product following organomercurial activation.
    J Biol Chem. 1989 Jan 25;264(3):1353-6 PMID: 2536363
  53. Mr 92,000 gelatinase release correlates with the metastatic phenotype in transformed rat embryo cells.
    Cancer Res. 1990 Jul 1;50(13):3872-7 PMID: 2162246
  54. Independent expression and cellular processing of Mr 72,000 type IV collagenase and interstitial collagenase in human tumorigenic cell lines.
    Cancer Res. 1990 Oct 1;50(19):6184-91 PMID: 2169338
  55. Plasminogen-activator inhibitor type 1 is a potent natural inhibitor of extracellular matrix degradation by fibrosarcoma and colon carcinoma cells.
    Proc Natl Acad Sci U S A. 1990 Sep;87(18):6939-43 PMID: 2169614
  56. Increased expression of the Mr 72,000 type IV collagenase in human colonic adenocarcinoma.
    Cancer Res. 1991 Jan 1;51(1):439-44 PMID: 1846313
  57. 92-kD type IV collagenase mediates invasion of human cytotrophoblasts.
    J Cell Biol. 1991 Apr;113(2):437-49 PMID: 1849141
  58. Identification of the rat Heymann nephritis autoantigen (GP330) as a receptor site for plasminogen.
    J Biol Chem. 1991 Jun 15;266(17):10825-9 PMID: 1645711
  59. Plasminogen activation by receptor-bound urokinase. A kinetic study with both cell-associated and isolated receptor.
    J Biol Chem. 1991 Jul 5;266(19):12752-8 PMID: 1829461
Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1093/emboj/16.9.2319
Published
1997-05-01
Pages
2319-32
Language
English
Region
England
NLM ID
8208664
PMCID
PMC1169833
Subset
IM
External Links
PubMed source DOI: 10.1093/emboj/16.9.2319 PMC Full Text View journal details
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