Expression of membrane type 1 matrix metalloproteinase, matrix metalloproteinase 2 and tissue inhibitor of metalloproteinase 2 in human cartilaginous tumors with special emphasis on mesenchymal and dedifferentiated chondrosarcoma

1999 ◽  
Vol 125 (10) ◽  
pp. 541-548 ◽  
Author(s):  
Akio Sakamoto ◽  
Yoshinao Oda ◽  
Yukihide Iwamoto ◽  
Masazumi Tsuneyoshi
Keyword(s):  
Matrix Metalloproteinase ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Matrix Metalloproteinase 2 ◽  
Dedifferentiated Chondrosarcoma ◽  
Tissue Inhibitor ◽  
Membrane Type ◽  
Cartilaginous Tumors

scholarly journals TIMP-2 (tissue inhibitor of metalloproteinase-2) regulates MMP-2 (matrix metalloproteinase-2) activity in the extracellular environment after pro-MMP-2 activation by MT1 (membrane type 1)-MMP

2003 ◽  
Vol 374 (3) ◽  
pp. 739-745 ◽  
Author(s):  
M. Margarida BERNARDO ◽  
Rafael FRIDMAN
Keyword(s):  
Matrix Metalloproteinase ◽  
Extracellular Space ◽  
Ternary Complex ◽  
Plasma Membranes ◽  
Cancer Metastasis ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Matrix Metalloproteinase 2 ◽  
Tissue Inhibitor ◽  
Membrane Type

The matrix metalloproteinase (MMP)-2 has a crucial role in extracellular matrix degradation associated with cancer metastasis and angiogenesis. The latent form, pro-MMP-2, is activated on the cell surface by the membrane-tethered membrane type 1 (MT1)-MMP, in a process regulated by the tissue inhibitor of metalloproteinase (TIMP)-2. A complex of active MT1-MMP and TIMP-2 binds pro-MMP-2 forming a ternary complex, which permits pro-MMP-2 activation by a TIMP-2-free neighbouring MT1-MMP. It remains unclear how MMP-2 activity in the pericellular space is regulated in the presence of TIMP-2. To address this question, the effect of TIMP-2 on MMP-2 activity in the extracellular space was investigated in live cells, and their isolated plasma membrane fractions, engineered to control the relative levels of MT1-MMP and TIMP-2 expression. We show that both free and inhibited MMP-2 is detected in the medium, and that the net MMP-2 activity correlates with the level of TIMP-2 expression. Studies to displace MT1-MMP-bound TIMP-2 in a purified system with active MMP-2 show minimal displacement of inhibitor, under the experimental conditions, due to the high affinity interaction between TIMP-2 and MT1-MMP. Thus inhibition of MMP-2 activity in the extracellular space is unlikely to result solely as a result of TIMP-2 dissociation from its complex with MT1-MMP. Consistently, immunoblot analyses of plasma membranes, and surface biotinylation experiments show that the level of surface association of TIMP-2 is independent of MT1-MMP expression. Thus low-affinity binding of TIMP-2 to sites distinct to MT1-MMP may have a role in regulating MMP-2 activity in the extracellular space generated by the ternary complex.

scholarly journals Substrate choice of membrane-type 1 matrix metalloproteinase is dictated by tissue inhibitor of metalloproteinase-2 levels

2007 ◽  
Vol 98 (4) ◽  
pp. 563-568 ◽  
Author(s):  
Tomoya Kudo ◽  
Takahisa Takino ◽  
Hisashi Miyamori ◽  
Erik W. Thompson ◽  
Hiroshi Sato
Keyword(s):  
Matrix Metalloproteinase ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Tissue Inhibitor ◽  
Substrate Choice ◽  
Membrane Type
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