Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.17 (MMP-3)
 3,419 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The remodelling of extracellular matrix and angiogenesis represent two essential processes for tumor growth and metastatic dissemination. These phenomena imply many interactions between tumor cells and host cells via action of various proteases including metalloproteinases (MMPs) whose activity is controlled by TIMPs and serine proteases (tissue type Plasminogen Activator (tPA), urokinase type Plasminogen Activator (uPA) and plasmin) inhibited in particular by PAI-1 (Plasminogen Activator Inhibitor- 1). Evolution of tumors depends on the joint action of these enzymes, as well as precise balance between these proteases and their physiological inhibitors. Proteases regulate the fate and activity of many proteins by controlling appropriate intra- or extracellular localization; shedding from cell surfaces ; activation or inactivation of proteases and other enzymes, cytokines, hormones or growth factors and exposure of cryptic neoproteins. Hence, proteases initiate, modulate and terminate a wide range of important cellular functions by processing bioactive molecules an thereby control essential biological processes, such as DNA replication, cell-cycle progression, cell proliferation, differentiation and migration, morphogenesis and tissue remodelling, neuronal outgrowth, haemostasis, wound healing, immunity, angiogenesis and apoptosis. Work completed has for objective to elucidate the specific part played by serine proteases and MMPS produced by the host cells in the processes of tumor growth and angiogenesis. By using an original model of transplantation of malignant murine keratinocytes (PDVA cell line) into deficient mice (-/-) and wild type mice (+/+), we showed the essential proteolytic role of PAI-1 produced by host cells in the tumor progression and angiogenesis. This mechanism of PAI-1 action was confirmed by using the model in vitro aorta rings. By using deficient mice for one or two MMPs combined (MMP-2, MMP-3, MMP-9, MMP-11, MMP-2&9, MMP3&9), we demonstrated that only the combined deficiency of MMP-2 and -9 showed an absence of tumor invasion and angiogenesis. These data suggest the existence of compensatory mechanisms of a MMP by another MMP or another proteolytic way. These phenomena of redundancy are to be known and detailed to elaborate in a near future, the development of specific inhibitors of MMPS.
Bull Mem Acad R Med Belg 2006
PMID:[Roles of serine proteases and matrix metalloproteinases in tumor invasion and angiogenesis]. 1728 5

The present investigation combined a classical conditioning paradigm with a head-shake response (HSR) habituation task in order to evaluate the importance of dorsal hippocampal neural plasticity to spontaneous recovery. In the first experiment animals exhibited rapid HSR habituation (air stimulus to the ear) and an 85% level of spontaneous recovery following a 24 h inter-session interval. The addition of a brief tone prior to the air stimulus produced a similar pattern of habituation during the first session, but the level of spontaneous recovery was reduced (44%) during Session II. In a second experiment dorsal hippocampal lesioned rats placed on this tone/HSR paradigm responded with an 87% level of spontaneous recovery during Session II; while neocortex lesioned control rats indicated significantly reduced levels of spontaneous recovery (55%). In a third experiment bilateral injections of a general MMP inhibitor, FN-439, into the dorsal hippocampus resulted in high levels of spontaneous recovery (81%); while control rats injected with artificial cerebrospinal fluid displayed a significant attenuation of spontaneous recovery (45%). Finally, animals bilaterally injected with a specific MMP-3 inhibitor into the dorsal hippocampus indicated very similar results to those obtained following FN-439 injection. These findings indicate that animals prepared with dorsal hippocampal lesions, or injections with an MMP inhibitor, revealed an impaired association between the tone and air stimulus thus maximum spontaneous recovery was present 24 h later. Thus, it appears that the dorsal hippocampus influences habituation by conserving responses and reducing spontaneous recovery when a temporally contingent signaling cue is present.
Neurobiol Learn Mem 2009 Nov
PMID:Influence of dorsal hippocampal lesions and MMP inhibitors on spontaneous recovery following a habituation/classical conditioning head-shake task. 1957 15