Critical appraisal of the use of matrix metalloproteinase inhibitors in cancer treatment
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...Similarly, clinical trials on MMP inhibitors (MMPIs) in late-stage cancer patients have yielded an inconsistent outcome — in most cases, significant progression occurs despite MMPI treatmen...
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Cites background from "Critical appraisal of the use of ma..."
...…of MMPs and serine proteases has prompted an unexpectedly weak benefit in some animal tumor models as well as clinical trials in humans, suggesting that a principal dissemination capacity remained intact (Della et al., 1999; Zucker et al., 2000; Kruger et al., 2001; Coussens et al., 2002)....
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...mechanism upon protease inhibitor–based treatment of progressive cancer disease (Zucker et al., 2000; Kruger et al., 2001; Coussens et al., 2002)....
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...…dissemination may represent a candidate escape Th e Jo ur na l o f C el l B io lo gy Mesenchymal–amoeboid transition in tumor cells | Wolf et al. 275 mechanism upon protease inhibitor–based treatment of progressive cancer disease (Zucker et al., 2000; Kruger et al., 2001; Coussens et al., 2002)....
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...In vivo, protease inhibitor–based targeting of MMPs and serine proteases has prompted an unexpectedly weak benefit in some animal tumor models as well as clinical trials in humans, suggesting that a principal dissemination capacity remained intact (Della et al., 1999; Zucker et al., 2000; Kruger et al., 2001; Coussens et al., 2002)....
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References
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"Critical appraisal of the use of ma..." refers background in this paper
...MMPs are transcribed and secreted by the constitutive secretory pathway, except in the case of neutrophils, macrophages (Birkedal-Hansen et al., 1993), and Paneth cells (Lopez-Boado et al., 2000); these cells store MMPs in secretory granules....
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...Activated MMPs are modulated by endogenous proteinase inhibitors including TIMP-1, -2, -3, -4 which speci®cally regulate MMPs in tissues and a2macroglobulin (a2-M), which is a broad-spectrum protease inhibitor prominently displayed in plasma (Birkedal-Hansen et al., 1993; Stetler-Stevenson, 1999)....
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...All MMPs share several highly conserved domains, including an activation locus [PRCGXPD] in the amino-terminal `pro' domain and a zinc atom binding domain [VAAHExGHxxGxxH] in the active site (catalytic domain), with three histidines coordinating the zinc (Birkedal-Hansen et al., 1993)....
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...Activation of MMPs is achieved by removal of the N-terminal prosequence of approximately 80 amino acids to yield mature enzyme (Birkedal-Hansen et al., 1993)....
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...A subset of six membrane type MMPs (MT-MMPs) contain a transmembrane domain of approximately 20 amino acids which attaches the enzymes to the cell surface and a short cytoplasmic domain (Sato et al., 1994) which is involved in intracellular tra cking (Lehti et al., 2000; Nakahara et al., 1998)....
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...MT-MMPs activate proMMP-2 at the cell surface, leading to enhanced cellular invasion in vitro (Sato et al., 1994)....
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...MMPs containing a furin-like recognition domain (RXKR) in their propeptides, MMP-11, MMP-23 (Velasco et al., 1999), and MT-MMPs (Sato et al., 1994; Strongin et al., 1995) are activated intracellularly in the trans-Golgi network by a group of calcium-dependent transmembrane serine proteinases (furin/PACE/kex-2)....
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...The exception to the rule is that TIMP-1 is a poor inhibitor of MT-MMPs....
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...MMPs containing a furin-like recognition domain (RXKR) in their propeptides, MMP-11, MMP-23 (Velasco et al., 1999), and MT-MMPs (Sato et al., 1994; Strongin et al., 1995) are activated intracellularly in the trans-Golgi network by a group of calcium-dependent transmembrane serine proteinases…...
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1,879 citations
1,656 citations
"Critical appraisal of the use of ma..." refers background in this paper
...MMPs containing a furin-like recognition domain (RXKR) in their propeptides, MMP-11, MMP-23 (Velasco et al., 1999), and MT-MMPs (Sato et al., 1994; Strongin et al., 1995) are activated intracellularly in the trans-Golgi network by a group of calcium-dependent transmembrane serine proteinases…...
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1,578 citations
"Critical appraisal of the use of ma..." refers background in this paper
...…cDNA demonstrated that MMPs may act primarily to alter the extracellular environment to allow sustained growth in an ectopic site as opposed to having a speci®c role in allowing the cells to extravasate from the blood stream (Cameron et al., 2000; Chambers and Matrisian, 1997; Nelson et al., 2000)....
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