Plasmin and plasminogen activator inhibitor type 1 promote cellular motility by regulating the interaction between the urokinase receptor and vitronectin.
Journal of Clinical InvestigationPublished 1 July 1997Open access
David Waltz, Lisa Natkin, Ross M. Fujita, Ying Wei, Harold A. Chapman
Citations287
SJR quartileQ1
SJR score4.72
SNIP2.17
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TL;DR
A complex regulatory scheme for uPAR-dependent cellular adhesion to vitronectin is illuminated: Active urokinase promotes adhesion and also subsequent detachment through activation of plasmin or complex formation with PAI-1.
Abstract
The urokinase receptor (uPAR) coordinates plasmin-mediated cell-surface proteolysis and promotes cellular adhesion via a binding site for vitronectin on uPAR. Because vitronectin also binds plasminogen activator inhibitor type 1 (PAI-1), and plasmin cleavage of vitronectin reduces PAI-1 binding, we explored the effects of plasmin and PAI-1 on the interaction between uPAR and vitronectin. PAI-1 blocked cellular binding of and adhesion to vitronectin by over 80% (IC50 approximately 5 nM), promoted detachment of uPAR-bearing cells from vitronectin, and increased cellular migration on vitronectin. Limited cleavage of vitronectin by plasmin also abolished cellular binding and adhesion and induced cellular detachment. A series of peptides surrounding a plasmin cleavage site (arginine 361) near the carboxy-terminal end of vitronectin were synthesized. Two peptides spanning res 364-380 blocked binding of uPAR to vitronectin (IC50 approximately 8-25 microM) identifying this region as an important site of uPAR-vitronectin interaction. These data illuminate a complex regulatory scheme for uPAR-dependent cellular adhesion to vitronectin: Active urokinase promotes adhesion and also subsequent detachment through activation of plasmin or complex formation with PAI-1. Excess PAI-1 may also promote migration by blocking cellular adhesion and/or promoting detachment, possibly accounting in part for the strong correlation between PAI-1 expression and tumor cell metastasis.
Keywords
MedicineBiochemistry, Genetics and Molecular Biology
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Journal of Clinical InvestigationThe plasminogen activator/plasmin system.
1,180 Citations1991J D Vassalli, A P Sappino +1 more
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ScienceRegulation of Integrin Function by the Urokinase Receptor
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The Journal of Cell BiologyA cellular binding site for the Mr 55,000 form of the human plasminogen activator, urokinase.
716 Citations1985J D Vassalli, D Baccino +1 more
The results demonstrate the presence of a membrane receptor for Uk on monocytes and show a hitherto unknown function for the A chain of Uk: binding of secreted enzyme to its receptor results in Uk acting as a membrane protease.
NatureThe serpin PAI-1 inhibits cell migration by blocking integrin αvβ3 binding to vitronectin
679 Citations1996Steingrimur Stefansson, Daniel A. Lawrence
It is reported that vitronectin significantly enhances the migration of smooth muscle cells (SMCs), and that the specific VNR αvβ3 is required for cell motility, and that PAI-1 can control cell–matrix interactions by regulating the accessibility of specific cell-attachment sites.
Journal of Biological ChemistryIdentification of the urokinase receptor as an adhesion receptor for vitronectin.
589 Citations1994Ying Wei, David Waltz +4 more
It is reported that the urokinase receptor (uPAR) is also a high affinity (Kd < 30 nM) receptor for vitronectin, indicating a duality in function for the receptor that intrinsically links matrix adhesion to regulation of protease activity.
Journal of Biological ChemistryCellular receptor for urokinase plasminogen activator. Carboxyl-terminal processing and membrane anchoring by glycosyl-phosphatidylinositol
578 Citations1991Michael Ploug, Ebbe Rønne +4 more
The cellular receptor for human urokinase-type plasminogen activator (u-PAR) is shown by several independent criteria to be a true member of a family of integral membrane proteins, anchored to the plasma membrane exclusively by a COOH-terminal glycosyl-phosphatidylinositol moiety.
Nature MedicineImpaired wound healing in mice with a disrupted plasminogen gene
565 Citations1996John Rømer, Thomas H. Bugge +5 more
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Journal of Clinical InvestigationBleomycin-induced pulmonary fibrosis in transgenic mice that either lack or overexpress the murine plasminogen activator inhibitor-1 gene.
561 Citations1996Daniel T. Eitzman, Ronald D. McCoy +5 more
Data demonstrate a direct correlation between the genetically determined level of PAI-1 expression and the extent of collagen accumulation that follows inflammatory lung injury and strongly support the hypothesis that alterations in fibrinolytic activity influenceThe extent of pulmonary fibrosis that occurs after inflammatory injury.
Cell Structure and FunctionNovel purification of vitronectin from human plasma by heparin affinity chromatography.
515 Citations1988Takemi Yatohgo, Masako Izumi +2 more
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Journal of Biological ChemistryPurification and characterization of a plasminogen activator inhibitor 1 binding protein from human plasma. Identification as a multimeric form of S protein (vitronectin).
486 Citations1988Paul Declerck, M De Mol +6 more
The gel filtration behavior, mobility on sodium dodecyl sulfate-gel electrophoresis, and concentration in plasma suggest that PAI-1-BP is a multimer (presumably a dimer) of S protein accounting for approximately 35% of the S protein in plasma.
The Journal of Cell BiologyThe receptor for urokinase type plasminogen activator polarizes expression of the protease to the leading edge of migrating monocytes and promotes degradation of enzyme inhibitor complexes.
473 Citations1990Anne Estreicher, Judith Mühlhauser +3 more
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The Journal of Cell BiologyThe plasminogen system and cell surfaces: evidence for plasminogen and urokinase receptors on the same cell type.
460 Citations1986EF Plow, D E Freaney +2 more
The results indicate that the two cell lines possess specific binding sites for plasminogen and urokinase, and a family of widely distributed cellular receptors for these components may be considered.
The Journal of Cell BiologyIs plasminogen activator inhibitor-1 the molecular switch that governs urokinase receptor-mediated cell adhesion and release?
456 Citations1996G Deng, Scott A. Curriden +3 more
A dynamic regulatory role for PAI-1 and uPA in uPAR-mediated cell adhesion and release is suggested, and may help to explain why high PAi-1 levels indicate a poor prognosis for many cancers.
Journal of Clinical InvestigationGlioblastoma expression of vitronectin and the alpha v beta 3 integrin. Adhesion mechanism for transformed glial cells.
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Evidence is provided for a cell adhesion mechanism in glioblastoma tumors that might potentiate gliOBlastoma cell invasion of normal brain.
BioEssaysUrokinase and urokinase receptor: A paracrine/autocrine system regulating cell migration and invasiveness
399 Citations1993Francesco Blasi
PubMedHigh levels of urokinase-type plasminogen activator and its inhibitor PAI-1 in cytosolic extracts of breast carcinomas are associated with poor prognosis.
390 Citations1993J Grøndahl-Hansen, I. J. Christensen +5 more
It is suggested that PAI-1 plays a role in protecting the tumor against degrading itself and may be a biochemical marker of tumor angiogenesis, in good agreement with the supposed function of uPA in cancer invasion.
Proceedings of the National Academy of SciencesPrevention of metastasis by inhibition of the urokinase receptor.
382 Citations1993Craig Crowley, Robert L. Cohen +4 more
The results indicate that cell surface u-PA activity is essential to the metastatic process and the assay system employed in these experiments may be generally useful in testing other therapeutic modalities to limit the spread of primary tumors.
Breast Cancer Research and TreatmentUrokinase (uPA) and its inhibitor PAI-1 are strong and independent prognostic factors in node-negative breast cancer
361 Citations1993F. Jänicke, Manfred Schmitt +5 more
The combination of uPA and PAI-1 in the group of patients with axillary node-negative breast cancer allows us to identify the 45 percent of patients having an increased risk of relapse and thus would possibly be candidates for being spared the necessity of adjuvant therapy.
Annual Review of Cell BiologyThe Directed Migration of Eukaryotic Cells
309 Citations1986Sherwin J. Singer, Abraham Kupfer
The in vivo migration of eukaryotic cells over surfaces is important to a wide range of physiological processes, such as the development of the embryo, defense against infections, wound healing, the homing of lym phocytes to lymphoid organs, and tumor metastases.
New England Journal of MedicineDepressed Bronchoalveolar Urokinase Activity in Patients with Adult Respiratory Distress Syndrome
268 Citations1990Paul Bertozzi, Birgir Astedt +5 more
Increased antifibrinolytic activity due to both urokinase inhibitors and antiplasmins in the bronchoalveolar compartment of patients with ARDS contributes to the formation and persistence of hyaline membranes, a key component of alveolar histopathology in ARDS.
Experimental Cell ResearchThe Urokinase Receptor Is a Major Vitronectin-Binding Protein on Endothelial Cells
247 Citations1996Sandip M. Kanse, Christine Kost +3 more
The interaction of VN with the u-PA receptor may be involved in the regulation of cellular processes necessary for endothelial cell invasion and migration at VN-rich extracellular matrix sites.
PubMedUrokinase receptor antagonists inhibit angiogenesis and primary tumor growth in syngeneic mice.
246 Citations1996H Y Min, Laura V. Doyle +5 more
Findings suggest that urokinase receptor antagonists may be useful therapeutically as inhibitors of tumor progression and in vivo, basic fibroblast growth factor-induced neovascularization and B16 melanoma growth in syngeneic mice are substantially suppressed by these molecules.
The EMBO JournalMolecular evolution of plasminogen activator inhibitor‐1 functional stability.
224 Citations1995Mitchell B. Berkenpas, Daniel A. Lawrence +1 more
The nature of the identified mutations implies that the unique instability of the PAI‐1 active conformation evolved through global changes in protein packing and suggest a selective advantage for transient inhibitor function.
Journal of Biological ChemistryReversible cellular adhesion to vitronectin linked to urokinase receptor occupancy.
213 Citations1994David Waltz, Harold A. Chapman
It is reported that cytokine-stimulated human myelomonocytic cells express a divalent cation- and Arg-Gly-Asp-independent high affinity receptor for urea-purified vitronectin (Kd < 10 nM).
Journal of Biological ChemistryDomain structure of vitronectin. Alignment of active sites.
181 Citations1984Shintaro Suzuki, Michael D. Pierschbacher +4 more
The results show that the biological activities of vitronectin are located in distinct parts of both of the vitronECTin polypeptides, which appear to be identical except for the presence of an additional 10-kDa fragment near or at the COOH terminus of the 75-k da polyPEptide.
BloodMac-1 (CD11b/CD18) and the urokinase receptor (CD87) form a functional unit on monocytic cells
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PAI-1 is a potentially important prognostic factor in pulmonary adenocarcinoma and may as such be used to select patients with low stage and poor prognosis for adjuvant therapy subsequent to complete surgical resection.
Journal of Clinical InvestigationExpression of plasminogen activator inhibitor type 1 by human prostate carcinoma cells inhibits primary tumor growth, tumor-associated angiogenesis, and metastasis to lung and liver in an athymic mouse model.
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The Journal of Cell BiologyMetastatic behavior of human melanoma cell lines in nude mice correlates with urokinase-type plasminogen activator, its type-1 inhibitor, and urokinase-mediated matrix degradation.
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PubMedBinding of urokinase to its receptor promotes migration and invasion of human melanoma cells in vitro.
154 Citations1994Andreas Stahl, Barbara M. Mueller
It is demonstrated that a highly metastatic melanoma cell line (M24met) that secretes uPA expresses high levels of the uPA receptor (uPAR), and that uPA contributes to at least two important steps in this process, matrix dissolution and migration.
FEBS LettersReceptor‐mediated endocytosis of plasminogen activators and activator/inhibitor complexes
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International Journal of CancerCo‐expression of urokinase, urokinase receptor and PAI‐1 is necessary for optimum invasiveness of cultured lung cancer cells
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Biochemical and Biophysical Research CommunicationsUrokinase-Urokinase Receptor Interaction: Non-Mitogenic Signal Transduction in Human Epidermal Cells
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International Journal of CancerPlasminogen activator system in human breast cancer
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American Journal of Physiology-Cell PhysiologyUrokinase receptor mediates mechanical force transfer across the cell surface
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65 Citations1994Cornelis F.M. Sier, H J Vloedgraven +9 more
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Cell Differentiation and DevelopmentInteractions between type 1 plasminogen activator inhibitor, extracellular matrix and vitronectin
61 Citations1990Dietmar Seiffert, Jun Mimuro +2 more
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European Journal of BiochemistryLimited Plasmin Proteolysis of Vitronectin
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PubMedExpression of plasminogen activators and their inhibitors in human pancreatic carcinoma: immunohistochemical study.
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It is concluded that immunohistochemical analysis of PAI-2 expression in pancreatic carcinomas may yield important prognostic information.
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Journal of Biological ChemistryEnergetics of Leukocyte Integrin Activation
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CR3-mediated binding and detachment of cells is not driven by a reversible change in affinity but by two mechanistically distinct processes, an energetically neutral activation step for binding and an energy-dependent step that reverses binding of ligand.
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