Abstract
Tissue inhibitors of metalloproteinases (TIMPs) are endogenous inhibitors of matrix metalloproteinases (MMPs) and the balance between MMPs/TIMPs regulates the extracellular matrix (ECM) turnover and remodeling during normal development and pathogenesis. Increasing evidence indicates a much more complex role for TIMPs during tumor progression and angiogenesis, in addition to their regulation of MMP-mediated ECM degradation. In this article, we review both the MMP-dependent and -independent actions of TIMPs for the regulation of cell death, cell proliferation, and angiogenesis, with a particular emphasis on TIMP-1 in the regulation of tetraspanin/integrin-mediated cell survival signal transduction pathways.
Publication types
-
Research Support, N.I.H., Extramural
-
Review
MeSH terms
-
Animals
-
Antigens, CD / metabolism
-
Apoptosis
-
Cell Proliferation
-
Cell Survival
-
Disease Progression
-
Humans
-
Integrin beta1 / metabolism
-
Matrix Metalloproteinase Inhibitors
-
Mice
-
Models, Biological
-
Neoplasms / enzymology*
-
Neoplasms / pathology
-
Neovascularization, Pathologic / metabolism
-
Platelet Membrane Glycoproteins / metabolism
-
Prognosis
-
Signal Transduction*
-
Tetraspanin 30
-
Tissue Inhibitor of Metalloproteinase-1 / physiology*
-
Tissue Inhibitor of Metalloproteinases / physiology*
Substances
-
Antigens, CD
-
CD63 protein, human
-
Cd63 protein, mouse
-
Integrin beta1
-
Matrix Metalloproteinase Inhibitors
-
Platelet Membrane Glycoproteins
-
Tetraspanin 30
-
Tissue Inhibitor of Metalloproteinase-1
-
Tissue Inhibitor of Metalloproteinases