• Biomedical Science Letters
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• v.20 no.3
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• pp.103-110
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• 2014

Matrix metalloproteinases (MMPs), also called matrixins, function in the extracellular environment of cells and degrade both matrix and non-matrix proteins. They are multidomain proteins and their activities are regulated by tissue inhibitor of metalloproteinases (TIMPs). The uncontrolled regulation of MMPs is involved in various pathologic processes, such as tumor invasion, migration, host immune escape, extravasation, angiogenesis, and tumor growth. Especially, matrix metalloproteinase-9 (MMP-9) is one of the metastasis-accelerating genes involved in metastasis of various types of human cancers. Here, we review the member of MMP family and discusses their domain structure and function, enzyme activation, the mechanism of inhibition by TIMPs. In particular, we focus the role of MMP-9 in relation to cancer metastasis.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.7
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• pp.3259-3264
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• 2012

Curcumin (CM) possesses anti-cancer activity against a variety of tumors. Matrix metalloproteinases (MMPs) play an important role in remodeling the extracellular matrix and their activities are regulated by tissue inhibitor of metalloproteinases (TIMPs) family. Control of MMP and TIMP activity are now of great significance. In this study, the effect of CM is investigated on metastatic MMPs and anti-metastatic TIMPs genes on MDA breast cancer cells cultured in a mixture of DMEM and Ham's F12 medium and treated with different concentrations of CM (10, 20 and $40{\mu}M$ for various lengths of time. Reverse transcription followed by quantitative real time PCR was used to detect the gene expression levels of MMPs and TIMPs in CM-treated versus untreated cases and the data were analyzed by one-way ANOVA. At high concentrations of curcumin, TIMP-1, -2, -3 and -4 genes were up-regulated after 48 hours of treatment, their over-expression being accompanied by down-regulation of MMP-2 and MMP-9 gene expression levels in a concentration- and time-dependent manner. These results suggest that curcumin plays a role in regulating cell metastasis by inhibiting MMP-2 and MMP-9 and up-regulating TIMP1 and TIMP4 gene expression in breast cancer cells.

• Asian-Australasian Journal of Animal Sciences
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• v.27 no.11
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• pp.1526-1531
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• 2014

Matrix metalloproteinases (MMP) are key enzymes involved in cell and tissue remodeling during ovarian follicle development and ovulation. The control of MMP9 transcription in ovarian follicles occurs through a core promoter region (-2,400 to -1,700 bp). The aim of this study was to screen genetic variations in the core promoter region and examine MMP9 transcription regulation and reproduction performance. A single cytosine deletion/insertion polymorphism was found at -1954 $C^+/C^-$. Genetic association analysis indicated significant correlation between the deletion genotype ($C^-$) with total egg numbers at 28 weeks (p = 0.031). Furthermore, luciferase-reporter assay showed the deletion genotype ($C^-$) had significantly lower promoter activity than the insertion genotype ($C^+$) in primary granulosa cells (p<0.01). Therefore, the identified polymorphism could be used for marker-assisted selection to improve chicken laying performance.

• Biomedical Science Letters
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• v.9 no.3
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• pp.123-131
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• 2003

Inflammation appears to have a major role in the development of atherosclerosis. Cyclooxygenase-2 (COX-2) is involved in the inflammatory response via the generation of prostanoids that, in turn, are involved in the production of matrix metalloproteinases (MMPs). This study hypothesized that a vascular infection with cytomegalovirus (CMV) may induce a chronic inflammatory reaction and activated inflammatory cells may express inflammatory mediators such as cyclooxygenase-2 (COX-2) and matrix metalloproteinases-9 (MMP-9). To confirm the hypothesis, the immunohistochemical stains for CMV late antigen, COX-2, MMP-9, macrophage, and T-lymphocyte were performed on CMV-infected atherosclerotic lesions. The immunoreactivity for COX-2 and MMP-9 was evident in all cases of atherosclerosis along with plaques, mainly in macrophages/foamy cells, intimal and medial smooth muscle cells, and endothelial cells of the intima. Within the intima, the increased immunoreactivity for COX-2 and MMP-9 was colocalized to the area stained with CMV late antigen. Sections from control specimens showed no immunoreactivity for CMV late antigen, COX-2 and MMP-9. These data seem to support the hypothesis that CMV may participate in a pathogenetic mechanism for atherogenesis or progression of atherosclerosis.

• Journal of Integrative Natural Science
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• v.4 no.4
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• pp.255-265
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• 2011

Marine ecosystems are often characterized by a high biological diversity, and it corresponds to a high chemical diversity. Up to present, more than 20,000 new bioactive substances have been isolated from marine organisms, where considerable numbers of these naturally occurring derivatives are developed as potential candidates for pharmaceutical application. In this process, screening of natural products from marine organisms that could potentially inhibit the expression of metalloproteinases has gained a huge popularity. Cancer is considered as one of the deadliest diseases in the medical field. Matrix metalloproteinase (MMPs) can degrade extracellular matrix (ECM) components and play important roles in a variety of biological and pathological processes. Matrix metalloproteinase inhibitors (MMPIs) have been identified as potential therapeutic candidates for metastasis, arthritis, chronic inflammation and wrinkle formation.

• Biomedical Science Letters
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• v.10 no.2
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• pp.143-151
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• 2004

Matrix metalloproteinases (MMPs) are capable of degrading extracellular matrix, a process that is necessary for angiogenesis, tumor invasion and metastasis. Platelet-activating factor (PAP) increases angiogenesis, tumor growth and metastasis through nuclear factor (NF)-$\kappa$B activation. Based on these facts, the involvement of MMPs in PAF-induced pulmonary metastasis was investigated in murine sarcoma cells, MMSV-BALB/3T3. Messenger RNA expression and enzymatic activity of MMP-9 were assessed by RT-PCR and zymography, and cell migration and metastasis were done for the detection of MMP-9 functional activity. PAP induced mRNA expression and enzymatic activity of MMP-9, and its effects were either inhibited by the PAP antagonist, WEB 2170 or by the NF-$\kappa$B inhibitor, parthenolide, or p65 antisense oligonucleotide in a dose-dependent manner. In addition, PAF induced promoter activity of MMP-9, which was inhibited by WEB 2170, phenanthroline, NAC, PDTC. These results indicate that PAF induces mRNA expression and enzymatic activity of MMP-9 in NF-$\kappa$B dependent manner. Cell migration assay showed that PAF induced MMSV-BALB/3T3 migration, and its effect was significantly inhibited by treatment with phenanthroline. PAF enhanced pulmonary metastasis of murine sarcoma cells, MMSV-BALB/3T3 was also reduced by phenanthroline. These results suggest that PAF-enhanced cell migration and pulmonary metastasis is mediated through the expression of MMP. In conclusion, It is suggested that PAF enhances pulmonary metastasis by inducing MMP-9 expression via the activation of NF-$\kappa$B.

• Journal of Life Science
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• v.22 no.7
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• pp.964-969
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• 2012

Genistein, a predominant isoflavone, has been shown to inhibit the growth of various cancer cells in vitro and in vivo without toxicity to normal cells. In the present study, we investigated the effects of genistein on the activity and the expression of matrix metalloproteinases (MMPs) in MCF-7 and MDA-MB-231 human breast adenocarcinoma cells. Our findings showed that MMP-9 and -2 activation was significantly increased in response to 12-O-tetradecanoyl phorbol-13-acetate (TPA). However, the increased activities of MMP-9 and -2 in TPA-treated cells were concentration-dependently inhibited by treatment with genistein, and this was also correlated with a decrease in the expression of their mRNA and proteins. In addition, a matrigel invasion assay showed that genistein reduced TPA-induced invasion of MCF-7 and MDA-MB-231 cells. Although further in vivo studies are needed, these results suggest that genistein treatment may inhibit tumor cell invasion and, therefore, act as a dietary source to decrease the risk of cancer metastasis.

• Journal of Korean Neurosurgical Society
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• v.50 no.4
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• pp.288-292
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• 2011

Objective : Matrix metalloproteinases (MMPs), especially MMP-2 and MMP-9 have been known to play an important role in secondary inflammatory reaction after spinal cord injury (SCI). The aim of this study was to investigate the expression and activity of MMP-2 and MMP-9 and to determine their relationship with disruption of endothelial blood-barrier after photochemically induced SCI in rats. Methods : Female Sprague-Dawley rats, weighing between 250 and 300 g (aged 8 weeks) received focal spinal cord ischemia by photothrombosis using Rose Bengal. Expressions and activities of MMP-2 and MMP-9 were assessed by Western blot and gelatin zymography at various times from 6 h to 7 days. Endothelial blood-barrier integrity was assessed indirectly using spinal cord water content. Results : Zymography and Western blot analysis demonstrated rapid up-regulation of MMP-9 protein levels in spinal cord after ischemic onset. Expressions and activities of MMP-9 showed a significant increased at 6 h after the photothrombotic ischemic event, and reached a maximum level at 24 h after the insult. By contrast, activated MMP-2 was not detected at any time point in either the experimental or the control groups. When compared with the control group, a significant increase in spinal cord water content was detected in rats at 24 h after photothrombotic SCI. Conclusion : Early up-regulation of MMP-9 might be correlated with increased water content in the spinal cord at 24 h after SCI in rats. Results of this study suggest that MMP-9 is the key factor involved in disruption of the endothelial blood-barrier of the spinal cord and subsequent secondary damage after photothrombotic SCI in rats.

• Reproductive and Developmental Biology
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• v.34 no.1
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• pp.55-62
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• 2010

Matrix metalloproteinases (MMP) play important roles in extracellular matrix (ECM) remodeling during ovarian follicular development, oocytes development and ovulation. In an attempt to investigate the effect of MMP activation in development cumulus-oocytes complexes, we examined the localization and expression of MMP, and monitored MMP expression profile. Cumulus-oocytes complexes were collected and matured in vitro for 24 hr, 36 hr and 48 hr. A mRNA expression of MMP-2, MMP-9, TIMP-2 and TIMP-3 was detected in all culture medium regardless of CC, DC and CDCs. Activity of MMP-2 in the DC progressively was increased from 24 hr to 48 hr. But MMP-9 was not detected in all culture medium. The localization of MMP-2 was also measured by immunohistochemistry analysis. The MMP-2 and TIMP-2 was detected in cumulus cell and oocyte zone pellucida. Expression of MMP-2 protein in the COCs was progressively increased from 24 hr to 48 hr. However, MMP-9 protein was progressively decreased from 24 hr to 48 hr. And TIMP-2 protein was most highly expressed in the CDCs 36 hr. Expression of TIMP-3 protein in the CDCs was progressively increased from 24 hr to 48 hr. In conclusion, these results suggest that MMP-2 plays a role in maintaining normal maturation and development by controlling the ECM inhibitor concentration on cumulus cell and oocytes.

• Journal of Physiology & Pathology in Korean Medicine
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• v.22 no.6
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• pp.1470-1474
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• 2008

This study was performed to examine the anti-metastatic effect of ethanol extract of Samguikoeui-Tang (SGKE), a formula consisting of four oriental herbs, in highly-metastatic HT1080 human fibrosarcoma cells. SGKE significantly inhibited the adhesion of HT1080 cells to matrigel at nontoxic concentrations in a dose-dependent manner, while it did not exert cytotoxicity against HT1080 cells up to the concentration of 100 ${\mu}g$/ml. Also, SGKE depressed the activity of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) by gelatin zymography. However, SGKE did not affect the mRNA expression of MMP-2 and TIMP-2, an inhibitor of MMP-2, by RT-PCR analysis. In addition, the effect of SGKE on HT1080 cell invasion was determined using Boyden chamber assay. SGKE suppressed the invasion of HT1080 cells in a dose-dependent manner. Taken together, these results suggest that SGKE has an anti-metastatic effect via inhibition of MMP-2 and -9 activities.