Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.35 (matrix metalloproteinase 9)
 2,207 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A proform of high molecular weight type IV collagenase was isolated and purified 1230-fold from human metastatic carcinoma tissue. Like matrix metalloproteinases (MMPs), the enzyme was activated by trypsin and degraded type IV collagen and gelatin at a neutral pH, the activity was inhibited by EDTA and o-phenanthroline. However, the molecular weight was much higher than MMPs which degraded type IV collagen, gelatinase A (MMP-2; 72 kDa gelatinase/type IV collagenase) (EC 3.4.24.24), gelatinase B (MMP-9; 92 kDa gelatinase/type IV collagenase) (EC 3.4.24.35), stromelysin-1 (MMP-3; 57 kDa) (EC 3.4.24.17) and stromelysin-2 (MMP-10; 57 kDa) (EC 3.4.24.22). The other significant difference from MMPs was that the enzyme was not activated by 4-aminophenylmercuric acetate nor inhibited by TIMP. Taking together these results, this high molecular weight type IV collagenase might be a newly found enzyme different from MMPs or might have the same configuration as MMPs already reported.
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PMID:Isolation and characterization of a high molecular weight type IV collagenase isolated from human carcinoma tissue. 838 26

The response of human T lymphocytes to various stimuli includes the expression of the matrix metalloproteinase (MMP) genes stromelysin 2, gelatinase A and gelatinase B. The proteins encoded by these genes could confer the capacity to degrade macromolecular components of the extracellular matrix (ECM), and to shed transmembrane proteins such as tumor necrosis factor (TNF), TNF receptor, Interleukin-6 receptor and Fas ligand. To identify further MMP genes transcribed in T lymphocytes exposed to phorbol 12-myristate 13-acetate and a calcium ionophore, we combined reverse transcription and polymerase chain reaction using primers specific for conserved domains and detected collagenase 3 transcripts, first described in a human breast cancer. However, when the sequence of the complementary DNA was compared, additional 23 nucleotides were found in the 5' nontranslated region of the lymphocyte messenger RNA (mRNA). Northern blot analysis revealed 2 major inducible mRNA species of 1.9 and 2.8 kilobases, whose levels were lower than those of stromelysin 2. The observation that activated T lymphocytes transcribe several MMP genes, including a collagenase, indicates that the effector functions of these cells include enzymatic activities towards most constituents of the ECM, as well as some transmembrane proteins relevant to inflammation and apoptosis.
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PMID:A matrix metalloproteinase gene expressed in human T lymphocytes is identical with collagenase 3 from breast carcinomas. 956 63

Matrix metalloproteinases (MMP) are a family of zinc-dependent enzymes which degrade various components of the extracellular matrix (ECM) and play an important role in facilitating neoplastic cell invasion and metastasis. Structural changes in the extracellular matrix are necessary for cell migration during tissue remodeling and tumor invasion. Expression of MMP-2, -3, -9, -10, and -13 was investigated in both spontaneous and xenografted (cells derived from an established cell-line [DAOY#3]) childhood medulloblastomas (MEDs)/primitive neuroectodermal tumors (PNETs) employing an indirect alkaline phosphatase conjugated immunocytochemical technique. Evaluation of the results was based on (a) the percent of neoplastically transformed tissue that reacted positively and (b) a measure of staining intensity [graded from A (highest) to D]. The two forms of stromelysin (SL), types 1 (MMP-3) and 2 (MMP-10), share 82% sequence homology, but exhibit differences in cellular synthesis and inducibility by cytokines and growth factors in vitro. Strong overall expression of MMP-3 and -10 was found only in the spontaneous MEDs/PNETs, especially in the ECM adjacent to blood vessels. Positive immunoreactivity could be seen for these two MMPs in the ECM surrounding over 90% of the neoplastically transformed cells in the spontaneous cases, and the staining intensity was also the strongest possible (A,B). Focal (surrounding less than 10% of the neoplastically transformed cells) but strong (A,B) immunoreactivity for collagenase-3 (MMP-13) was also only detected in spontaneous MEDs/PNETs, an endopeptidase characterized by a potent degrading activity against a wide spectrum of substrates. Weak (surrounding anywhere between 10% and 90% of the neoplastically transformed cells, and of B and B,C intensity) expression of MMP-2 (gelatinase A) and MMP-9 (gelatinase B), two cytokine-induced MMPs, was also observed in the spontaneous cases. Staining for MMP-2 was negative in the xenografted MEDs/PNETs. The only positive immunoreactivity in the xenografted MEDs/PNETs was observed in the case of MMP-9, with expression of strong intensity in the ECM surrounding over 90% of the neoplastically transformed xenografted MED/PNET cells (++++; A,B). It is clear that the activation of MMPs and their inhibitors occurs in a very well orchestrated manner. The data presented here suggest that there are significant differences in the pathophysiology of spontaneous and xenografted human neoplasms, which further establishes the already detected limitations of such models in preclinical cancer research.
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PMID:Significant differences in the matrix metalloproteinase expression profiles of spontaneous medulloblastomas/primitive neuroectodermal tumors as compared with their xenografted, established tumor cell line derived counterparts. 1121 45

The matrix metalloproteinases (MMPs) are a family of enzymes that degrade the extracellular matrix (ECM) and are considered to be important in neoplastic cell invasion and metastasis. Structural changes in the extracellular matrix are necessary for cell migration during tissue remodeling and neoplastic invasion. Expression of MMP-2, -3, -9, -10, and -13 was investigated in human childhood medulloblastomas (MEDs)/primitive neuroectodermal tumors (PNETs) employing an indirect alkaline phosphatase conjugated immunohistochemical antigen detection technique. Evaluation of the results was based on (a) the percent of neoplastically transformed tissue that reacted positively and (b) a measure of immunoreactivity or staining intensity [graded from A (highest) to D (negative)]. Strong overall expression of MMP-3 and -10 was found in MEDs/PNETs, especially in the ECM adjacent to blood vessels. Positive immunoreactivity was identified for these two MMPs in the ECM surrounding over 90% of the neoplastically transformed cells with the staining intensity being also the strongest possible (A,B). These two forms of stromelysin (SL), types 1 (MMP-3) and 2 (MMP-10), share 82% sequence homology, but exhibit differences in cellular synthesis and inducibility by cytokines and growth factors in vitro. Focal (surrounding less than 10% of the neoplastically transformed cells) but strong (A,B) immunoreactivity was determined for collagenase-3 (MMP-13), an endopeptidase characterized by a potent degrading activity against a wide spectrum of substrates. Weak (surrounding anywhere between 10% and 90% of the neoplastically transformed cells, and of B and B,C intensity) expression of MMP-2 (gelatinase A) and MMP-9 (gelatinase B), two cytokine-induced MMPs, was also observed. It is clear that the activation of MMPs and their inhibitors occurs in a very well orchestrated manner. The necessity of these same enzymes for the extravasation and infiltration of lymphocytes into regions of chronic local inflammation, as associated with neoplastically transformed masses of cells, may aid the transformed cells which have already acquired a more aggressive, metastatic immunophenotype (IP) to enter the peripheral circulation. Further characterization of the expression and utilization of MMPs and their inhibitors in the progression of solid human malignancies should lead to the development of novel anti-cancer therapies.
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PMID:Matrix metalloproteinase expression in childhood medulloblastomas/primitive neuroectodermal tumors. 1121 44

The matrix metalloproteinases (MMPs) are a family of enzymes that degrade the extracellular matrix (ECM) and are considered to be important in neoplastic cell invasion and metastasis. Structural changes in the extracellular matrix are necessary for cell migration during tissue remodeling and neoplastic cell invasion. Histochemical expression of MMP-2, -3, -9, -10, and -13 was observed in 19 human colorectal carcinomas (CCs) employing an indirect alkaline phosphatase (AP) conjugated antigen detection technique. Evaluation of the results was based on (a) the percent of neoplastically transformed cells that reacted positively and (b) a measure of staining intensity [graded from A (highest) to D]. The two forms of stromelysin (SL), types 1 (MMP-3) and 2 (MMP-10), share 82% sequence homology, but exhibit differences in cellular synthesis and inducibility by cytokines and growth factors in vitro. Strong overall expression of MMP-3 and -10 was found in all CC cases observed, especially in the ECM adjacent to blood vessels. Positive immunoreactivity could be seen for these two MMPs in the ECM surrounding over 90% of the neoplastically transformed cells, and the staining intensity was also the strongest possible (A,B). Weak (surrounding anywhere between 10% and 90% of the neoplastically transformed cells, and of strong A,B intensity) expression of MMP-2 (gelatinase A) and MMP-9 (gelatinase B), two cytokine-induced MMPs, was also observed in CCs. Expression of collagenase-3 (MMP-13), an endopeptidase characterized by a potent degrading activity against a wide spectrum of substrates, was not defined in the CCs cases observed by us. It is clear that the activation of MMPs and their inhibitors occurs in a very well orchestrated manner. The necessity of these same enzymes for the extravasation and infiltration of lymphocytes into regions of chronic local inflammation, as associated with neoplastically transformed masses of cells, may aid the transformed cells which have already acquired a metastatic immunophenotype to enter the peripheral circulation. Further characterization of the expression and utilization of MMPs and their inhibitors in the progression of solid human neoplasms should lead to the development of novel anti-cancer therapies.
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PMID:Prognostic significance of matrix metalloproteinase expression in colorectal carcinomas. 1121 43

The extracellular matrix metalloproteases (MMPs) secreted by various human tumor cells play a crucial role in tumor cell invasion and metastasis, but their expression in malignant mesothelioma (MM) cells has not been examined. In this study, we have investigated the spectrum of MMPs and tissue inhibitors of metalloproteases (TIMPs) produced by 8 MM cell lines. Using RT-PCR, we found that all investigated MM cell lines expressed genes encoding mRNA for MMP-1 (interstitial collagenase), MMP-2 (gelatinase A), MMP-3 (stromelysin-1), MMP-9 (gelatinase B) and TIMPs 1, 2 and 3. We also found that 6/8 MM cell lines expressed MMP-7 (matrilysin) and 3/8 MM cell lines expressed MMP-10 (stromelysin-2). MMP-11 (stromelysin-3) was not detected in any of the MM cell lines. Production of MMP-2 and MMP-9 was confirmed using gelatin zymography. In addition, all MM cell lines secreted a 66 kDa metalloprotease, while 3/8 MM cell lines secreted 46, 48, 51 and 63 kDa metalloproteases which specifically degraded the extracellular matrix components fibronectin, vitronectin and laminin. The 66 kDa protease was identified as MMP-3 by Western blot. Our results reveal a broad spectrum of MMPs and TIMPs produced by MM cells and indicate that different substrate specificities of MMPs may play a role in MM cell invasion.
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PMID:Expression and activity of matrix metalloproteases in human malignant mesothelioma cell lines. 1126 73

Previous work has shown that endothelial cell (EC)-derived matrix metalloproteinases (MMPs) regulate regression of capillary tubes in vitro in a plasmin- and MMP-1 dependent manner. Here we report that a number of serine proteases can activate MMP-1 and cause capillary tube regression; namely plasma kallikrein, trypsin, neutrophil elastase, cathepsin G, tryptase and chymase. Plasma prekallikrein failed to induce regression without coactivators such as high molecular weight kininogen (HMWK) or coagulation Factor XII. The addition of trypsin, the neutrophil serine proteases (neutrophil elastase and cathepsin G) and the mast cell serine proteases (tryptase and chymase) each caused MMP-1 activation and collagen type I proteolysis, capillary tubular network collapse, regression and EC apoptosis. Capillary tube collapse is accompanied by collagen gel contraction, which is strongly related to the wound contraction that occurs during regression of granulation tissue in vivo. We also report that proMMP-10 protein expression is markedly induced in ECs undergoing capillary tube morphogenesis. Addition of each of the serine proteases described above led to activation of proMMP-10, which also correlated with MMP-1 activation and capillary tube regression. Treatment of ECs with MMP-1 or MMP-10 siRNA markedly delayed capillary tube regression, whereas gelatinase A (MMP-2), gelatinase B (MMP-9) and stromelysin-1 (MMP-3) siRNA-treated cells behaved in a similar manner to controls and regressed normally. Increased expression of MMP-1 or MMP-10 in ECs using recombinant adenoviral delivery markedly accelerated serine protease-induced capillary tube regression. ECs expressing increased levels of MMP-10 activated MMP-1 to a greater degree than control ECs. Thus, MMP-10-induced activation of MMP-1 correlated with tube regression and gel contraction. In summary, our work demonstrates that MMP-1 zymogen activation is mediated by multiple serine proteases and MMP-10, and that these events are central to EC-mediated collagen degradation and capillary tube regression in 3D collagen matrices.
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PMID:MMP-1 activation by serine proteases and MMP-10 induces human capillary tubular network collapse and regression in 3D collagen matrices. 1587 Jan 7

Background: Matrix metalloproteinases (MMPs) are pleiotropic enzymes involved in extracellular protein degradation and turnover. MMPs are implicated in the pathogenesis of many neurological diseases, including multiple sclerosis (MS). Objective: To search the level of MMPs in the cerebrospinal fluid (CSF) of MS patients and detect possible disease-specific patterns. Methods: CSF samples from 32 MS patients and, from 15 control subjects with other inflammatory neurological diseases (OIND) were analyzed. The Bio-Plex Pro Human MMP 9-Plex Panel (Bio-Rad) was used for the quantification of MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-10, MMP-12, and MMP-13. Results: CSF MMP-1 and MMP-12 levels were significantly reduced in MS as compared with OIND. In MS patients' CSF: (i) MMP-1 levels were significantly higher in women vs. men; (ii) MMP-10 concentrations were higher in patients with CSF-restricted IgG oligoclonal bands, and (iii) MMP-7 levels were increased in patients with longer disease duration. In the OIND group MMP-7 and MMP-12 levels significantly and directly correlated with age. Conclusions: Our study contributes to investigating the role of MMPs in MS, with regard to CSF immunological features and disease duration. Sex-specific differences were also detected in MMPs CSF levels.
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PMID:Multiplex Matrix Metalloproteinases Analysis in the Cerebrospinal Fluid Reveals Potential Specific Patterns in Multiple Sclerosis Patients. 3061 40

The ability to accurately measure multiple proteins simultaneously in a single assay has the potential to markedly improve the efficiency of clinical tests composed of multiple biomarkers. We investigated the diagnostic accuracy of the two multiplex protein array platforms for detecting a bladder-cancer-associated diagnostic signature in samples from a cohort of 80 subjects (40 with bladder cancer). Banked urine samples collected from Kyoto and Nara Universities were compared to histologically determined bladder cancer. The concentrations of the 10 proteins (A1AT; apolipoprotein E-APOE; angiogenin-ANG; carbonic anhydrase 9-CA9; interleukin 8-IL-8; matrix metalloproteinase 9-MMP-9; matrix metalloproteinase 10-MMP10; plasminogen activator inhibitor 1-PAI-1; syndecan-SDC1; and vascular endothelial growth factor-VEGF) were monitored using two prototype multiplex array platforms and an enzyme-linked immunosorbent assay (ELISA) according to the manufacturer's technical specifications. The range for detecting each biomarker was improved in the multiplex assays, even though the lower limit of quantification (LLOQ) was typically lower in the commercial ELISA kits. The area under the receiver operating characteristics (AUROC) of the prototype multiplex assays was reported to be 0.97 for the multiplex bead-based immunoassay (MBA) and 0.86 for the multiplex electrochemoluminescent assay (MEA). The sensitivities and specificities for MBA were 0.93 and 0.95, respectively, and for MEA were 0.85 and 0.80, respectively. Accuracy, positive predictive values (PPV), and negative predictive values (NPV) for MBA were 0.94, 0.95, and 0.93, respectively, and for MEA were 0.83, 0.81, and 0.84, respectively. Based on these encouraging preliminary data, we believe that a multiplex protein array is a viable platform that can be utilized as an efficient and highly accurate tool to quantitate multiple proteins within biologic specimens.
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PMID:Comparison of Commercial ELISA Kits, a Prototype Multiplex Electrochemoluminescent Assay, and a Multiplex Bead-Based Immunoassay for Detecting a Urine-Based Bladder-Cancer-Associated Diagnostic Signature. 3167 75