Active and Tissue Inhibitor of Matrix Metalloproteinase-free Gelatinase B Accumulates within Human Microvascular Endothelial Vesicles*

Human gelatinase B is involved in tissue remodeling and angiogenesis. It is thought to be synthesized and rapidly secreted as an inactive precursor. In this report, we have shown that human endothelial cells accumulate active forms of gelatinase B in the cytosol. Microvascular but not macrovascular endothelial cells dramatically increased the expression of cytosolic gelatinase B in response to phorbol myristate acetate. Western blotting showed that tissue inhibitor of metalloproteinase-1 (TIMP1) was also present in the cytosol. Whereas gelatinase B was complexed with TIMP1 in the conditioned medium, it existed as a free enzyme in the cytosol, suggesting that the formation of gelatinase B and TIMP1 complex occurs after their secretion. Immunogold electron microscopy revealed that gelatinase B was localized in secretory vesicles which were especially prominent in invading pseudopodia. In contrast, TIMP1 was found throughout the cytoplasm but was not present in the gelatinase vesicles. The accumulation of intracellular activated gelatinase B, ready for rapid release, may facilitate the migration of microvascular endothelial cells during angiogenesis.

• Publication year

  1998

• Venue

  Journal of Biological Chemistry

• Publication date

  1998-02-27

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1074/JBC.273.9.5400PMID 9479001
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Matrix degrading metalloproteinases

  2005cited by this paper
• Gelatinases A and B.

  2002cited by this paper
• Involvement of PA/plasmin system in the processing of pro‐MMP‐9 and in the second step of pro‐MMP‐2 activation

  1997cited by this paper
• Urokinase Plasminogen Activator and Gelatinases Are Associated with Membrane Vesicles Shed by Human HT1080 Fibrosarcoma Cells*

  1997cited by this paper
• Human microvascular endothelial cells differ from macrovascular endothelial cells in their expression of matrix metalloproteinases.

  1997cited by this paper
• Localization of Matrix Metalloproteinase MMP-2 to the Surface of Invasive Cells by Interaction with Integrin αvβ3

  1996cited by this paper
• Membrane-type matrix metalloproteinases (MT-MMPs) in tumor metastasis.

  1996cited by this paper
• Expression, subcellular distribution and plasma membrane binding of cathepsin B and gelatinases in bone metastatic tissue.

  1996cited by this paper
• Transmembrane-deletion Mutants of the Membrane-type Matrix Metalloproteinase-1 Process Progelatinase A and Express Intrinsic Matrix-degrading Activity (*)

  1996cited by this paper
• Plasminogen activators and matrix metalloproteinases in angiogenesis.

  1996cited by this paper
• Angiogenesis: a paradigm for balanced extracellular proteolysis during cell migration and morphogenesis.

  1996cited by this paper
• Localization of matrix metalloproteinase MMP-2 to the surface of invasive cells by interaction with integrin alpha v beta 3.

  1996cited by this paper
• Preferential Inactivation of Tissue Inhibitor of Metalloproteinases-1 That Is Bound to the Precursor of Matrix Metalloproteinase 9 (Progelatinase B) by Human Neutrophil Elastase (*)

  1995cited by this paper
• Plasma membrane‐dependent activation of gelatinase A in human vascular endothelial cells

  1995cited by this paper
• Mechanism Of Cell Surface Activation Of 72-kDa Type IV Collagenase

  1995cited by this paper
• Furin-dependent intracellular activation of the human stromelysin-3 zymogen

  1995cited by this paper
• Activation of progelatinase B (MMP-9) by gelatinase A (MMP-2).

  1995cited by this paper
• Activation of the 92-kDa Gelatinase by Stromelysin and 4-Aminophenylmercuric Acetate

  1995cited by this paper
• Cell surface binding of TIMP‐2 and pro‐MMP‐2/TIMP‐2 complex

  1995cited by this paper
• Angiogenesis in cancer, vascular, rheumatoid and other disease

  1995cited by this paper
• Enhanced expression of tissue inhibitor of metalloproteinase‐2 (TIMP‐2) in the stroma of breast carcinomas correlates with tumor recurrence

  1994cited by this paper
• Excess matrix accumulation in scleroderma is caused partly by differential regulation of stromelysin and TIMP-1 synthesis.

  1994cited by this paper
• Structural and functional heterogeneity among peroxidase-negative granules in human neutrophils: identification of a distinct gelatinase-containing granule subset by combined immunocytochemistry and subcellular fractionation.

  1993cited by this paper
• Regulation of matrix metalloproteinase expression in human vein and microvascular endothelial cells. Effects of tumour necrosis factor alpha, interleukin 1 and phorbol ester.

  1993cited by this paper
• 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.

  1992cited by this paper
• The matrix‐degrading metalloproteinases

  1992cited by this paper
• Matrix metalloproteinase 3 (stromelysin) activates the precursor for the human matrix metalloproteinase 9.

  1992cited by this paper
• Matrix metalloproteinase 9 (92-kDa gelatinase/type IV collagenase) from HT 1080 human fibrosarcoma cells. Purification and activation of the precursor and enzymic properties.

  1992cited by this paper
• Human 92- and 72-kilodalton type IV collagenases are elastases.

  1991cited by this paper
• Binding of human endothelium to Ulex europaeus I-coated Dynabeads: application to the isolation of microvascular endothelium.

  1990cited by this paper
• SV40-transformed human lung fibroblasts secrete a 92-kDa type IV collagenase which is identical to that secreted by normal human macrophages.

  1989cited by this paper
• Tissue inhibitor of metalloproteinase (TIMP-2). A new member of the metalloproteinase inhibitor family.

  1989cited by this paper
• Secretion of metalloproteinases by stimulated capillary endothelial cells. I. Production of procollagenase and prostromelysin exceeds expression of proteolytic activity.

  1986cited by this paper
• Tumor-promoting phorbol esters induce angiogenesis in vitro.

  1985cited by this paper
• Double immunocytochemical labeling applying the protein A-gold technique.

  1982cited by this paper
• An endothelial cell growth factor from bovine hypothalamus: identification and partial characterization.

  1979cited by this paper
• Culture of human endothelial cells derived from umbilical veins. Identification by morphologic and immunologic criteria.

  1973cited by this paper

• A new approach towards developing a smart and multifunctional peptide-based drug delivery system for selective targeting and treatment of invasive/metastatic breast cancer.

  2026cites this paper
• Cancer Metastasis: The Role of the Extracellular Matrix and the Heparan Sulfate Proteoglycan Perlecan

  2020cites this paper
• Matrix Metalloproteinase-9 (MMP-9) as a Cancer Biomarker and MMP-9 Biosensors: Recent Advances

  2018cites this paper
• Pituitary adenylate cyclase-activating polypeptide ameliorates vascular dysfunction induced by hyperglycaemia

  2018cites this paper
• Impact of exogenous adrenocorticotropic hormone on gelatinase expression and steroidogenesis in the newly formed corpus luteum in sows

  2018cites this paper
• Microparticles: From Biogenesis to Biomarkers and Diagnostic Tools in Cardiovascular Disease.

  2016cites this paper
• SRC kinase inhibition with saracatinib limits the development of osteolytic bone disease in multiple myeloma

  2016cites this paper
• Microparticles: A Pivotal Nexus in Vascular Homeostasis and Disease.

  2016cites this paper
• Uric Acid Promotes Left Ventricular Diastolic Dysfunction in Mice Fed a Western Diet

  2015cites this paper
• Nitric oxide-matrix metaloproteinase-9 interactions: biological and pharmacological significance--NO and MMP-9 interactions.

  2014cites this paper
• Regulation of Proteolysis in Vascular Remodeling

  2014cites this paper
• The role of the haemodynamic Palladin protein within the Vasculature

  2014cites this paper
• Molecular basis of cell migration inhibition by the dietary phytochemical piperine

  2014cites this paper
• Potent tumor targeting drug release system comprising MMP-2 specific peptide fragment with self-assembling characteristics

  2014cites this paper
• Matrix metalloproteinase-9: Many shades of function in cardiovascular disease.

  2013cites this paper
• Evolving role of microparticles in the pathophysiology of endothelial dysfunction.

  2013cites this paper
• Role of Transglutaminase 2 in vascular remodeling

  2011cites this paper
• Transglutaminase 2 is secreted from smooth muscle cells by transamidation-dependent microparticle formation

  2011cites this paper
• Crucial role of HSP90 in the Akt-dependent promotion of angiogenic-like effect of glucose-regulated protein94 (Grp94)-IgG complexes

  2011cites this paper
• Modulation of metalloproteinase-9 in U87MG glioblastoma cells by A3 adenosine receptors.

  2010cites this paper
• Intracellular substrate cleavage: a novel dimension in the biochemistry, biology and pathology of matrix metalloproteinases

  2010cites this paper
• Cross-talk between vascular endothelial growth factor and matrix metalloproteinases in the induction of neovascularization in vivo.

  2010cites this paper
• Influência dos hormônios sexuais femininos sobre a inflamação alérgica pulmonar em modelo murino de asma crônica.

  2010cites this paper
• Antimetastatic Therapy in Colorectal Cancer: Role of Tumor Cell Matrix Metalloproteinase 9 (Methodology)

  2009cites this paper
• Higher Prevalence of Secretory CSE1L/CAS in Sera of Patients with Metastatic Cancer

  2009cites this paper
• Altered apoptosis of inflammatory neutrophils in MMP-9-deficient mice is due to lower expression and activity of caspase-3.

  2009cites this paper
• Cell-derived microparticles in haemostasis and vascular medicine

  2009cites this paper
• Interleukin-21 controls inflammatory pathways in IBD

  2009cites this paper
• Endothelial microparticles: a universal marker of vascular health?

  2009cites this paper
• CSE1L/CAS, the cellular apoptosis susceptibility protein, enhances invasion and metastasis but not proliferation of cancer cells

  2008cites this paper
• Roles of molecules involved in epithelial/mesenchymal transition during angiogenesis.

  2008cites this paper
• MMP‐2 expression precedes the final ripening process of the bovine cervix

  2008cites this paper
• The role of mast cells in ischemic and hemorrhagic brain injury

  2008cites this paper
• Matrix metalloproteinases and inflammatory diseases of the central nervous system

  2008cites this paper
• Microvesicles in the venom of Crotalus durissus terrificus (Serpentes, Viperidae).

  2007cites this paper
• Dendritic Cell Transmigration through Brain Microvessel Endothelium Is Regulated by MIP-1α Chemokine and Matrix Metalloproteinases1

  2007cites this paper
• Identification of a novel 82 kDa proMMP-9 species associated with the surface of leukaemic cells: (auto-)catalytic activation and resistance to inhibition by TIMP-1.

  2007cites this paper
• Kaposi’s Sarcoma-Associated Herpesvirus Infection Promotes Invasion of Primary Human Umbilical Vein Endothelial Cells by Inducing Matrix Metalloproteinases (cid:1)

  2007cites this paper
• Matrix metalloproteinases: new routes to the use of MT1-MMP as a therapeutic target in angiogenesis-related disease.

  2007cites this paper
• Kaposi's Sarcoma-Associated Herpesvirus Infection Promotes Invasion of Primary Human Umbilical Vein Endothelial Cells by Inducing Matrix Metalloproteinases

  2007cites this paper
• Immunohistochemical expression of matrix metalloproteinase‐2 and ‐9 in melanocytic nevi is altered by ultraviolet B

  2007cites this paper
• Metalloproteinases Chemokine and Matrix a MIP-1Microvessel Endothelium Is Regulated by Dendritic Cell Transmigration through Brain

  2006cites this paper
• Unusual presentation of digestive tumour

  2006cites this paper
• Matrix metalloproteinases and diseases of the central nervous system with a special emphasis on ischemic brain.

  2006cites this paper
• Control of matrix metalloproteinase production in human intestinal fibroblasts by interleukin 21

  2006cites this paper
• Making the cut: protease-mediated regulation of angiogenesis.

  2006cites this paper
• BARX2 and estrogen receptor-α (ESR1) coordinately regulate the production of alternatively spliced ESR1 isoforms and control breast cancer cell growth and invasion

  2006cites this paper
• Targeting matrix metalloproteases to improve cutaneous wound healing

  2006cites this paper
• Up-regulation of Matrix Metalloproteinase-9 in Smooth Muscle Cell Undergoing Death

  2006cites this paper
• Matrix metalloproteinases and angiogenesis

  2005cites this paper
• Diagnostic and prognostic value of angiogenesis-modulating genes in malignant thyroid neoplasms.

  2005cites this paper
• Invasion-associated MMP-2 and MMP-9 are Up-regulated Intracellularly in Concert with Apoptosis Linked to Melanoma Cell Detachment

  2005cites this paper
• Endometase/Matrilysin-2 in Human Breast Ductal Carcinoma in Situ and Its Inhibition by Tissue Inhibitors of Metalloproteinases-2 and -4

  2004cites this paper
• Vascular cell adhesion molecule 1 (VCAM-1) activation of endothelial cell matrix metalloproteinases: role of reactive oxygen species.

  2004cites this paper
• Inhibition of matrix metalloproteinase-9 reduces in vitro invasion and angiogenesis in human microvascular endothelial cells.

  2004cites this paper
• A dose-finding and pharmacokinetic study of the matrix metalloproteinase inhibitor MMI270 (previously termed CGS27023A) with 5-FU and folinic acid

  2004cites this paper
• Cell surface association of matrix metalloproteinase-9 (gelatinase B)

  2003cites this paper
• Influence of VEGF-R2 inhibition on MMP secretion and motility of microvascular human cerebral endothelial cells (HCEC)

  2003cites this paper
• Activation of Pro-gelatinase B by Endometase/Matrilysin-2 Promotes Invasion of Human Prostate Cancer Cells*

  2003cites this paper
• Adhesion molecules and matrix metalloproteinases in Multiple Sclerosis: effects induced by Interferon-beta.

  2003cites this paper
• The role of the matrix metalloproteinases in human endometrial and ovarian cycles.

  2003cites this paper
• Proteases in Tissue Remodelling of Lung and Heart

  2003cites this paper
• UNIVERSIDADE FEDERAL DO RIO GRANDE DO SUL FACULDADE DE MEDICINA PROGRAMA DE PÓS-GRADUAÇÃO EM MEDICINA: CIÊNCIAS MÉDICAS

  2003cites this paper
• Matrix Metalloproteinases and Myocardial Remodeling in Heart Failure

  2003cites this paper
• Constitutive secretion of MMP9 by early‐passage cultured human endothelial cells

  2003cites this paper
• Matrix Metalloproteinase (2, 9, and 14) Expression, Localization, and Activity in Ovine Corpora Lutea Throughout the Estrous Cycle1

  2002cites this paper
• Human retinal pigment epithelial lysis of extracellular matrix: functional urokinase plasminogen activator receptor, collagenase, and elastase.

  2002cites this paper
• CHAPTER 6 – ROLE OF MATRIX METALLOPROTEINASES AND PLASMINOGEN ACTIVATORS IN CANCER INVASION AND METASTASIS: THERAPEUTIC STRATEGIES

  2002cites this paper
• Possible role of matrix metalloproteinases in reconstruction of peripheral pulmonary arteries induced by hypoxia.

  2002cites this paper
• Shedding of the matrix metalloproteinases MMP-2, MMP-9, and MT1-MMP as membrane vesicle-associated components by endothelial cells.

  2002cites this paper
• Ovarian tissue remodeling: role of matrix metalloproteinases and their inhibitors.

  2002cites this paper
• Cyclooxygenase, lipoxygenase and tumor angiogenesis

  2002cites this paper
• Matrix Metalloproteinase Inhibition Prevents Oxidative Stress-Associated Blood–Brain Barrier Disruption after Transient Focal Cerebral Ischemia

  2001cites this paper
• The Role of Matrix Metalloproteinase Genes in Glioma Invasion: Co-dependent and Interactive Proteolysis

  2001cites this paper
• Matrix metalloproteinase expression by endothelial cells in collagen lattices changes during co‐culture with fibroblasts and upon induction of decorin expression

  2001cites this paper
• Matrix Metalloproteinases in Cancer

  2001cites this paper
• Matrix metalloproteinases in cancer invasion, metastasis and angiogenesis.

  2001cites this paper
• Metalloproteases and inhibitors in arthritic diseases.

  2001cites this paper
• Human endothelial gelatinases and angiogenesis.

  2001influential citation
• Curcuminoids Inhibit the Angiogenic Response Stimulated by Fibroblast Growth Factor-2, Including Expression of Matrix Metalloproteinase Gelatinase B*

  2000cites this paper
• Interplay of matrix metalloproteinases, tissue inhibitors of metalloproteinases and their regulators in cardiac matrix remodeling.

  2000cites this paper
• Xenopus laevis gelatinase B (Xmmp‐9): Development, regeneration, and wound healing

  2000cites this paper
• Overexpression of Copper and Zinc Superoxide Dismutase in Transgenic Mice Prevents the Induction and Activation of Matrix Metalloproteinases after Cold Injury-Induced Brain Trauma

  2000cites this paper
• Matrix metalloproteinases: pro- and anti-angiogenic activities.

  2000cites this paper
• Tumour vasculature as a target for anticancer therapy.

  2000cites this paper
• Posttranscriptional stimulation of endothelial cell matrix metalloproteinases 2 and 1 by endothelioma cells.

  2000cites this paper
• Physiological roles of matrix metalloproteinases: implications for tumor growth and metastasis.

  1999cites this paper
• Thrombin rapidly and efficiently activates gelatinase A in human microvascular endothelial cells via a mechanism independent of active MT1 matrix metalloproteinase.

  1999cites this paper
• Airway Epithelial Cell Migration Dynamics

  1999cites this paper
• Matrix Metalloproteinase 2 (MMP2) and MMP9 Are Produced by Kidney Collecting Duct Principal Cells but Are Differentially Regulated by SV40 Large-T, Arginine Vasopressin, and Epidermal Growth Factor*

  1999cites this paper
• Spotlight on microcirculation: an update.

  1999cites this paper
• Matrix metalloproteinase-19 in capillary endothelial cells: expression in acutely, but not in chronically, inflamed synovium.

  1999cites this paper
• MMP Inhibitors: Experimental and Clinical Studies

  1999cites this paper
• Activation of Matrix Metalloproteinase-9 (MMP-9) via a Converging Plasmin/Stromelysin-1 Cascade Enhances Tumor Cell Invasion*

  1999cites this paper
• Platelet-activating factor increases the expression of metalloproteinase-9 in human bronchial epithelial cells.

  1999cites this paper
• Early appearance of activated matrix metalloproteinase-9 and blood-brain barrier disruption in mice after focal cerebral ischemia and reperfusion.

  1999cites this paper