scholarly journals In Vitro Efficacy of a Sterically Stabilized Immunoliposomes Targeted to Membrane Type 1 Matrix Metalloproteinase (MT1-MMP)

2007 ◽  
Vol 30 (5) ◽  
pp. 972-978 ◽  
Author(s):  
Kazutaka Atobe ◽  
Tatsuhiro Ishida ◽  
Emi Ishida ◽  
Kouichi Hashimoto ◽  
Hideo Kobayashi ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Membrane Type

scholarly journals Membrane type-1 matrix metalloproteinase is induced following cyclic compression of in vitro grown bovine chondrocytes

2007 ◽  
Vol 15 (11) ◽  
pp. 1301-1310 ◽  
Author(s):  
J.N.A. De Croos ◽  
B. Jang ◽  
S.S. Dhaliwal ◽  
M.D. Grynpas ◽  
R.M. Pilliar ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Cyclic Compression ◽  
Membrane Type

scholarly journals Membrane type 1 matrix metalloproteinase (MT1-MMP) cleaves the recombinant aggrecan substrate rAgg1mut at the ‘aggrecanase’ and the MMP sites

1998 ◽  
Vol 333 (1) ◽  
pp. 159-165 ◽  
Author(s):  
Frank H. BÜTTNER ◽  
Clare E. HUGHES ◽  
Daniel MARGERIE ◽  
Andrea LICHTE ◽  
Harald TSCHESCHE ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Catalytic Domain ◽  
Human Articular Cartilage ◽  
Recombinant Enzymes ◽  
Recombinant Product ◽  
Weak Activity ◽  
Membrane Type

The recent detection of membrane type 1 matrix metalloproteinase (MT1-MMP) expression in human articular cartilage [Büttner, Chubinskaya, Margerie, Huch, Flechtenmacher, Cole, Kuettner, and Bartnik (1997) Arthritis Rheum. 40, 704–709] prompted our investigation of MT1-MMP's catabolic activity within the interglobular domain of aggrecan. For these studies we used rAgg1mut, a mutated form of the recombinant fusion protein (rAgg1) that has been used as a substrate to monitor ‘aggrecanase ’ catabolism in vitro [Hughes, Büttner, Eidenmüller, Caterson and Bartnik (1997) J. Biol. Chem. 272, 20269–20274]. The rAgg1 was mutated (G332 to A) to avoid the generation of a splice variant seen with the original genetic construct, which gave rise to heterogeneous glycoprotein products. This mutation yielded a homogeneous recombinant product. Studies in vitro with retinoic acid-stimulated rat chondrosarcoma cells indicated that the rAgg1mut substrate was cleaved at the ‘aggrecanase ’ site equivalent to Glu373-Ala374 (human aggrecan sequence enumeration) in its interglobular domain sequence segment. The differential catabolic activities of the recombinant catalytic domain (cd) of MT1-MMP and matrix metalloproteinases (MMPs) 3 and 8 were then compared by using this rAgg1mut as a substrate. Coomassie staining of rAgg1mut catabolites separated by SDS/PAGE showed similar patterns of degradation with all three recombinant enzymes. However, comparative immunodetection analysis, with neoepitope antibodies BC-3 (anti-ARGS …) and BC-14 (anti-FFGV …) to distinguish between ‘aggrecanase ’ and MMP-generated catabolites, indicated that the catalytic domain of MT1-MMP exhibited strong ‘aggrecanase ’ activity, cdMMP-8 weak activity and cdMMP-3 no activity. In contrast, cdMMP-3 and cdMMP-8 led to strongly BC-14-reactive catabolic fragments, whereas cdMT1-MMP resulted in weak BC-14 reactivity. N-terminal sequence analyses of the catabolites confirmed these results and also identified other potential minor cleavage sites within the interglobular domain of aggrecan. These results indicate that MT1-MMP is yet another candidate for ‘aggrecanase ’ activity in vivo.

scholarly journals Molecular Dissection of the Structural Machinery Underlying the Tissue-invasive Activity of Membrane Type-1 Matrix Metalloproteinase

2008 ◽  
Vol 19 (8) ◽  
pp. 3221-3233 ◽  
Author(s):  
Xiao-Yan Li ◽  
Ichiro Ota ◽  
Ikuo Yana ◽  
Farideh Sabeh ◽  
Stephen J. Weiss
Keyword(s):  
Matrix Metalloproteinase ◽  
Type I Collagen ◽  
Cell Function ◽  
Catalytic Domain ◽  
Transmembrane Domain ◽  
Type I ◽  
Cell Trafficking ◽  
Membrane Type

Membrane type-1 matrix metalloproteinase (MT1-MMP) drives cell invasion through three-dimensional (3-D) extracellular matrix (ECM) barriers dominated by type I collagen or fibrin. Based largely on analyses of its impact on cell function under two-dimensional culture conditions, MT1-MMP is categorized as a multifunctional molecule with 1) a structurally distinct, N-terminal catalytic domain; 2) a C-terminal hemopexin domain that regulates substrate recognition as well as conformation; and 3) a type I transmembrane domain whose cytosolic tail controls protease trafficking and signaling cascades. The MT1-MMP domains that subserve cell trafficking through 3-D ECM barriers in vitro or in vivo, however, remain largely undefined. Herein, we demonstrate that collagen-invasive activity is not confined strictly to the catalytic, hemopexin, transmembrane, or cytosolic domain sequences of MT1-MMP. Indeed, even a secreted collagenase supports invasion when tethered to the cell surface in the absence of the MT1-MMP hemopexin, transmembrane, and cytosolic tail domains. By contrast, the ability of MT1-MMP to support fibrin-invasive activity diverges from collagenolytic potential, and alternatively, it requires the specific participation of MT-MMP catalytic and hemopexin domains. Hence, the tissue-invasive properties of MT1-MMP are unexpectedly embedded within distinct, but parsimonious, sequences that serve to tether the requisite matrix-degradative activity to the surface of migrating cells.

Membrane type 1–matrix metalloproteinase (MT1-MMP) cooperates with sphingosine 1–phosphate to induce endothelial cell migration and morphogenic differentiation

Blood ◽  
2004 ◽  
Vol 103 (8) ◽  
pp. 3020-3028 ◽  
Author(s):  
Stéphanie Langlois ◽  
Denis Gingras ◽  
Richard Béliveau
Keyword(s):  
Cell Migration ◽  
Matrix Metalloproteinase ◽  
Endothelial Cell Migration ◽  
Bioactive Lipids ◽  
Aortic Endothelial Cells ◽  
Sphingosine 1 Phosphate ◽  
Gi Protein ◽  
Membrane Type

Abstract Membrane type 1–matrix metalloproteinase (MT1-MMP) has been suggested to play an important role in angiogenesis, but the mechanisms involved remain incompletely understood. Using an in vitro model of angiogenesis in which cell migration of bovine aortic endothelial cells (BAECs) and their morphogenic differentiation into capillary-like structures on Matrigel are induced by overexpression of MT1-MMP, we show that the platelet-derived bioactive lipid sphingosine 1–phosphate (S1P) is the predominant serum factor essential for MT1-MMP–dependent migration and morphogenic differentiation activities. In the presence of S1P, MT1-MMP–dependent cell migration and morphogenic differentiation were inhibited by pertussis toxin, suggesting the involvement of Gi-protein–coupled receptor-mediated signaling. Accordingly, cotransfection of BAECs with MT1-MMP and a constitutively active Gαi2 (Q205L) mutant increased cell migration and morphogenic differentiation, whereas treatment of BAECs overexpressing MT1-MMP with antisense oligonucleotides directed against S1P1 and S1P3, the predominant S1P receptors, significantly inhibited both processes. These results demonstrate that MT1-MMP–induced migration and morphogenic differentiation involve the cooperation of the enzyme with platelet-derived bioactive lipids through S1P-mediated activation of Gαi-coupled S1P1 and S1P3 receptors. Given the important contribution of platelets to tumor angiogenesis, the stimulation of endothelial MT1-MMP function by S1P may thus constitute an important molecular event linking hemostasis to angiogenesis. (Blood. 2004;103:3020-3028)

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