Matrix Metalloproteinases 2 and 9 in Avocation of Multitudinal Complications in Explicitly to Carcinoma: Review (original) (raw)
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Matrix metalloproteinases involvement in pathologic conditions
Rom J Morphol …, 2010
Matrix metalloproteinases (MMPs) have a great variability that provides a complex intervention in pathophysiological conditions. MMPs roles in pathology may be grouped into the following main types: (1) tissue destruction, as in cancer invasion and metastasis, rheumatoid arthritis, osteoarthritis, different types of ulcers, periodontal disease, brain injury and neuroinflammatory diseases; (2) fibrosis, as in liver cirrhosis, fibrotic lung disease, otosclerosis, atherosclerosis, and multiple sclerosis; (3) weakening of matrix, as in dilated cardiomyopathy, epidermolysis bullosa, aortic aneurysm and restenotic lesions. Recent data also adds new MMPs functions in angiogenesis and apoptosis. Interesting opposite intervention in escaping mechanisms vs. antitumor defensive mechanisms had been also reported. As MMP-7 is expressed by tumor cells of epithelial and mesenchymal origin, it may be used as a biological marker of an aggressive phenotype and as a target of therapeutic intervention. MMPs play a pivotal role in the pathogenesis of arthritis, atherosclerosis, pulmonary emphysema, and endometriosis. Although MMP involvement in pathology is more than simple excessive matrix degradation, or an imbalance between them and their specific tissular inhibitors (TIMPs), MMP inhibition may be of therapeutic benefit, so synthetic MMPs inhibitors had been developed and are currently under clinical testing.
Metalloproteinases of the extracellular matrix and their inhibitors
BioTechnologia, 2016
The dynamic equilibrium between the synthesis and degradation of the extracellular matrix is to a large extent mediated by matrix metalloproteinase (MMP) enzymes, which are antagonized by tissue inhibitors of metalloproteinases (TIMPs). Tissue-degrading enzymes of the metalloproteinase family have been implicated in the pathogenesis of several conditions involving the extracellular matrix. MMPs are a family of zinc-dependent endopeptidases capable of degrading practically all components of the extracellular matrix. Recent insights suggest that MMPs may also have a broader spectrum of functions, including regulation of the inflammatory response and cytokine signaling. MMPs have been subdivided according to their main degradation activity and the continuously growing list of known substrates. Metalloproteinases are promising drug targets, and they are subjected to pharmacological inhibition by clinically available drugs such as tetracyclines and bisphosphonates. Interest in MMPs has recently increased, because their expression is frequently related to tumor progression. As such, metalloproteinases have diagnostic potential as markers to predict the outcome of disease processes. This review introduces the members of the MMP family and discusses their domain structure and function, their significance in physiology and pathology and the mechanism of inhibition by TIMPs.
The Roles of Matrix Metalloproteinases and Their Inhibitors in Human Diseases
International Journal of Molecular Sciences
Matrix metalloproteinases (MMPs) are a family of zinc-dependent extracellular matrix (ECM) remodeling endopeptidases that have the capacity to degrade almost every component of the ECM. The degradation of the ECM is of great importance, since it is related to embryonic development and angiogenesis. It is also involved in cell repair and the remodeling of tissues. When the expression of MMPs is altered, it can generate the abnormal degradation of the ECM. This is the initial cause of the development of chronic degenerative diseases and vascular complications generated by diabetes. In addition, this process has an association with neurodegeneration and cancer progression. Within the ECM, the tissue inhibitors of MMPs (TIMPs) inhibit the proteolytic activity of MMPs. TIMPs are important regulators of ECM turnover, tissue remodeling, and cellular behavior. Therefore, TIMPs (similar to MMPs) modulate angiogenesis, cell proliferation, and apoptosis. An interruption in the balance between ...
Biological Activity and Clinical Implications of the Matrix Metalloproteinases
he family of human matrix metalloproteinases (MMPs) comprises several tightly regulated classes of proteases. These enzymes and their specific inhibitors play important roles in tumour progression and the metastatic process by facilitating extracellular matrix degradation. As scientific understanding of the MMPs has advanced, therapeutic strategies focusing on blocking these enzymes by matrix metalloproteinase inhibitors have rapidly developed. Low molecular weight tissue inhibitors of matrix metalloproteinase (TIMPs) represent a new therapeutic approach for the treatment of individual types of cancer. This paper aims to briefly summarize current knowledge about the role of MMPs in select non- tumorous lesions, tumor invasion and metastasis. The perspectives in therapeutic intervention in cancer are also mentioned. The role of MMPs in diagnosis and prognosis of colorectal and thyroid cancer is discussed in detail.
Annals of the New York Academy of Sciences, 1999
On the basis of the concept that MMPs synthesized in tissues seep into the bloodstream, we have examined MMP levels in the plasma of patients with cancer. In colorectal, breast, prostate, and bladder cancer, most patients with aggressive disease have increased plasma levels of gelatinase B. In patients with advanced colorectal cancer, high levels of either gelatinase B or TIMP complex were associated with shortened survival. We propose that these assays may be clinically useful in characterizing metastatic potential in selected kinds of cancer. In rheumatoid arthritis and systemic lupus erythematosus (SLE), serum and plasma levels of stromelysin-1 were ~3-5-fold increased. Fluctuating serum stromelysin-1 levels in SLE did not correspond with change in disease activity. In SLE, stromelysin-1 may be a component of the chronic tissue repair process rather than being responsible for inciting tissue damage. On the basis of these observations, we conclude that measurement of plasma/serum MMP and TIMP levels may provide important data for selecting and following patients considered for treatment with drugs that interfere with MMP activity.
Frontiers in Molecular Biosciences
Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases that regulate the turnover of extracellular matrix (ECM) components. Gross and La Piere discovered MMPs in 1962 during an experiment on tissue samples from a tadpole’s tail. Several subtypes of MMPs have been identified, depending on their substrate specificity and localization. MMPs are involved as essential molecules in multiple and diverse physiological processes, such as reproduction, embryonic development, bone remodeling, tissue repair, and regulation of inflammatory processes. Its activity is controlled at various levels such as at transcription level, pro-peptide activation level and by the activity of a family of tissue inhibitors of metalloproteinase, endogenous inhibitors of MMPs. Cancer metastasis, which is the spread of a tumor to a distant site, is a complex process that is responsible for the majority of cancer-related death It is considered to be an indicator of cancer metastasis. During metastasis, t...
Matrix Metalloproteinases and Cancer - Roles in Threat and Therapy
Asian Pacific Journal of Cancer Prevention, 2014
Matrix metalloproteinases (MMPs) are a family of zinc dependent extracellular matrix (ECM) remodelling endopeptidases having the ability to degrade almost all components of extracellular matrix and implicated in various physiological as well as pathological processes. Carcinogenesis is a multistage process in which alteration of the microenvironment is required for conversion of normal tissue to a tumour. Extracellular matrix remodelling proteinases such as MMPs are principal mediators of alterations observed in the microenvironment during carcinogenesis and according to recent concepts not only have roles in invasion or late stages of cancer but also in regulating initial steps of carcinogenesis in a favourable or unfavourable manner. Establishment of relationships between MMP overproduction and cancer progression has stimulated the development of inhibitors that block proteolytic activity of these enzymes. In this review we discuss the MMP general structure, classification, regulation roles in relation to hallmarks of cancer and as targets for therapeutic intervention.
Intricate functions of matrix metalloproteinases in physiological and pathological conditions
Journal of cellular physiology, 2016
Matrix metalloproteinases (MMPs) are a diverse group of proteolytic enzymes and play an important role in the degradation and remodeling of the extracellular matrix (ECM). In normal physiological conditions, MMPs are usually minimally expressed. Despite their low expression, MMPs have been implicated in many cellular processes ranging from embryological development to apoptosis. The activity of MMPs is controlled at three different stages: (1) transcription, (2) zymogen activation, and (3) inhibition of active forms by tissue inhibitor metalloproteinases (TIMPs). They can collectively degrade any component of ECM and basement membrane, and their excessive activity has been linked to numerous pathologies mainly including, but not limited to, tumor evasion and metastasis. The lack of information about several MMPs and the steady stream of new discoveries suggest that there is much more to be studied in this field. In particular, there is a need for controlling their expression in dise...
Clinical Chemistry and Laboratory Medicine, 2009
Matrix metalloproteinases (MMPs) are zinc-dependent enzymes capable of degrading components of the extracellular matrix during physiological and pathological processes. Of particular importance, altered concentrations of MMP-2 (gelatinase A, EC 3.4.24.24) and MMP-9 (gelatinase B, EC 3.4.24.35) have been reported to reflect important pathophysiological alterations in many disease conditions and in response to drug therapy (1-6). However, while circulating levels of MMPs, especially MMP-9, have been suggested to have diagnostic and prognostic value in many disease conditions, many authors have neglected preanalytical factors that can significantly affect measured concentrations of circulating MMPs and their endogenous inhibitors; the tissue inhibitors of metalloproteinases (TIMPs) (7). This is an important issue and many publications cast doubt on the validity of many previous studies that used serum instead of plasma to assess MMPs and TIMPs concentrations (7). We along with others have shown artificially higher MMP-9 concentrations in serum compared with plasma (7-9). Artificially higher MMP concentrations measured in clinical studies could hamper their diagnostic
The Role of Matrix Metalloproteinases in Human Body
Biology and Medicine
MMPs are Zn dependent proteases. All of MMPs kind is multi-domain proteins and their activities are regulated by tissue inhibitors of metalloproteinases. The prevention of the pathologies which is created by MMPs used some synthetic and naturally inhibitors. This review will explain the attitude MMPs and some chemical and physical factors which to being high level and low could affect to MMPs activity and synthesis as caffeine, one of snake venom components, melatonin, serotonin, stress factor, E and C vitamins.