|
|
|
|
|
||
|
|||||
| Home Help Feedback Subscriptions Archive Search Table of Contents | |||||
Journal of Cell Science, Vol 113, Issue 22 3979-3987, Copyright © 2000 by Company of Biologists
JOURNAL ARTICLES |
L Yan, MA Moses, S Huang and DE Ingber
Departments of Surgery and Pathology, Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
The growth and regression of capillary blood vessels during angiogenesis is greatly influenced by changes in the activity of matrix metalloproteinases (MMPs), which selectively degrade extracellular matrix (ECM) and thereby modulate capillary endothelial cell shape, growth and viability. However, changes in cell-ECM binding and cell spreading have also been reported to alter MMP secretion and activation. Studies were carried out to determine whether changes in integrin binding or cell shape feed back to alter MMP-2 processing in human capillary endothelial (HCE) cells. Catalytic processing of proMMP-2 to active MMP-2 progressively decreased when HCE cells were cultured on dishes coated with increasing densities of fibronectin (FN), which promote both integrin binding and cell spreading. Conversely, the highest levels of active MMP-2 were detected in round cells cultured on low FN. When measured 24 hours after plating, this increase in active MMP-2 was accompanied by a concomitant rise in mRNA and protein levels for the membrane-type 1 MMP (MT1-MMP), which catalyzes the cleavage of proMMP-2. To determine whether proMMP-2 processing was controlled directly by integrin binding or indirectly by associated changes in cell shape, round cells on low FN were allowed to bind to microbeads (4.5 microm diameter) coated with a synthetic RGD peptide or FN; these induce local integrin receptor clustering without altering cell shape. ProMMP-2 activation was significantly decreased within minutes after bead binding in these round cells, prior to any detectable changes in expression of MT1-MMP, whereas binding of beads coated with control ligands for other transmembrane receptors had no effect. This inhibitory effect was mimicked by microbeads coated with activating antibodies against alphaVbeta3 and beta1 integrins, suggesting a direct role for these cell-surface ECM receptors in modulating proMMP-2 activation. Similar inhibition of proMMP-2 processing by integrin binding, independent of cell spreading, was demonstrated in cells that were cultured on small, microfabricated adhesive islands that prevented cell spreading while presenting a high FN density directly beneath the cell. Interestingly, when spread cells were induced to round up from within by disrupting their actin cytoskeleton using cytochalasin D, proMMP-2 processing did not change at early times; however, increases in MT1-MMP mRNA levels and MMP-2 activation could be detected by 18 hours. Taken together, these results suggest the existence of two phases of MMP-2 regulation in HCE cells when they adhere to ECM: (1) a quick response, in which integrin clustering alone is sufficient to rapidly inhibit processing of proMMP-2 and (2) a slower response, in which subsequent cell spreading and changes in the actin cytoskeleton feed back to decrease expression of MT1-MMP mRNA and, thereby, further suppress cellular proteolytic activity.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati 
Twitter What's this?
This article has been cited by other articles:
|
|
 |
|
  J. Attia, K. Boumediene, J.P. Pujol, J.M. Valleton, E. Huet, and Q.T. Nguyen Matrix Gene Expression in Dermal Fibroblasts Cultured on Hyaluronan-coated Polysulfone Membranes Journal of Bioactive and Compatible Polymers, July 1, 2009; 24(4): 329 - 349. [Abstract] [PDF]
|
|
|
|
 |
|
 M. A. Lafleur, D. Xu, and M. E. Hemler Tetraspanin Proteins Regulate Membrane Type-1 Matrix Metalloproteinase-dependent Pericellular Proteolysis Mol. Biol. Cell, April 1, 2009; 20(7): 2030 - 2040. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Ispanovic, D. Serio, and T. L. Haas Cdc42 and RhoA have opposing roles in regulating membrane type 1-matrix metalloproteinase localization and matrix metalloproteinase-2 activation Am J Physiol Cell Physiol, September 1, 2008; 295(3): C600 - C610. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H.-Y. Lee, H.-J. You, J.-Y. Won, S.-W. Youn, H.-J. Cho, K.-W. Park, W.-Y. Park, J.-S. Seo, Y.-B. Park, K. Walsh, et al. Forkhead Factor, FOXO3a, Induces Apoptosis of Endothelial Cells Through Activation of Matrix Metalloproteinases Arterioscler Thromb Vasc Biol, February 1, 2008; 28(2): 302 - 308. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. K Parker and D. E Ingber Extracellular matrix, mechanotransduction and structural hierarchies in heart tissue engineering Phil Trans R Soc B, August 29, 2007; 362(1484): 1267 - 1279. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Sanka, R. Maddala, D. L. Epstein, and P. V. Rao Influence of Actin Cytoskeletal Integrity on Matrix Metalloproteinase-2 Activation in Cultured Human Trabecular Meshwork Cells Invest. Ophthalmol. Vis. Sci., May 1, 2007; 48(5): 2105 - 2114. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. E. Ingber Cellular mechanotransduction: putting all the pieces together again FASEB J, May 1, 2006; 20(7): 811 - 827. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Mehta and A. B. Malik Signaling Mechanisms Regulating Endothelial Permeability Physiol Rev, January 1, 2006; 86(1): 279 - 367. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Iyer, K. Pumiglia, and C. M. DiPersio {alpha}3{beta}1 integrin regulates MMP-9 mRNA stability in immortalized keratinocytes: a novel mechanism of integrin-mediated MMP gene expression J. Cell Sci., March 15, 2005; 118(6): 1185 - 1195. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. R. Polte, G. S. Eichler, N. Wang, and D. E. Ingber Extracellular matrix controls myosin light chain phosphorylation and cell contractility through modulation of cell shape and cytoskeletal prestress Am J Physiol Cell Physiol, March 1, 2004; 286(3): C518 - C528. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. W. Prager, J. M. Breuss, S. Steurer, J. Mihaly, and B. R. Binder Vascular endothelial growth factor (VEGF) induces rapid prourokinase (pro-uPA) activation on the surface of endothelial cells Blood, February 1, 2004; 103(3): 955 - 962. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. E. Ingber Mechanical Signaling and the Cellular Response to Extracellular Matrix in Angiogenesis and Cardiovascular Physiology Circ. Res., November 15, 2002; 91(10): 877 - 887. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. G. Galvez, S. Matias-Roman, M. Yanez-Mo, F. Sanchez-Madrid, and A. G. Arroyo ECM regulates MT1-MMP localization with {beta}1 or {alpha}v{beta}3 integrins at distinct cell compartments modulating its internalization and activity on human endothelial cells J. Cell Biol., November 7, 2002; 159(3): 509 - 521. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Samarakoon and P. J. Higgins MEK/ERK pathway mediates cell-shape-dependent plasminogen activator inhibitor type 1 gene expression upon drug-induced disruption of the microfilament and microtubule networks J. Cell Sci., January 8, 2002; 115(15): 3093 - 3103. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B.-K. Park, X. Zeng, and R. I. Glazer Akt1 Induces Extracellular Matrix Invasion and Matrix Metalloproteinase-2 Activity in Mouse Mammary Epithelial Cells Cancer Res., October 1, 2001; 61(20): 7647 - 7653. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. A. Rupp and C. D. Little Integrins in Vascular Development Circ. Res., September 28, 2001; 89(7): 566 - 572. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. S. Pepper Role of the Matrix Metalloproteinase and Plasminogen Activator-Plasmin Systems in Angiogenesis Arterioscler Thromb Vasc Biol, July 1, 2001; 21(7): 1104 - 1117. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Yan and M. A. Moses A Case of Tumor Betrayal : Biphasic Effects of TIMP-1 on Burkitt's Lymphoma Am. J. Pathol., April 1, 2001; 158(4): 1185 - 1190. [Full Text] [PDF]
|
|
|
|
 |
|
 J. Folkman Can mosaic tumor vessels facilitate molecular diagnosis of cancer? PNAS, January 16, 2001; 98(2): 398 - 400. [Full Text] [PDF]
|
|
|
|
 |
|
 L. Yan, N. Borregaard, L. Kjeldsen, and M. A. Moses The High Molecular Weight Urinary Matrix Metalloproteinase (MMP) Activity Is a Complex of Gelatinase B/MMP-9 and Neutrophil Gelatinase-associated Lipocalin (NGAL). MODULATION OF MMP-9 ACTIVITY BY NGAL J. Biol. Chem., September 28, 2001; 276(40): 37258 - 37265. [Abstract] [Full Text] [PDF]
|
|
