• Journal of Korean Traditional Oncology
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• v.15 no.1
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• pp.47-61
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• 2010

Objective : The aim of this present study is to evaluate the inhibitory effect of allergen removed Rhus verniciflua (ARV) on Matrix Metalloproteinase-9 (MMP-9), Matrix Metalloproteinase-2 (MMP-2) which is considered to have a clinically important role in tumor metastasis. Methods : The inhibitory effects of standardized extract of ARV on the MMP-2, MMP-9 were investigated by spectrofluorometer while the inhibitory effects on the active MMP-2, pro MMP-2, pro MMP-9 were investigated by zymography. Antimetastatic effect of standardized extract of ARV was investigated in vitro on human fibrosarcoma cell (HT1080)'s invasion through Matrigel. Results : The standardized extract of ARV showed inhibitory effects on the active MMP-2 (IC50, $1.01{\mu}g$/ml), active MMP-9 (IC50, $2.5{\mu}g$/ml) depending on concentrations which was determined by spectrofluorometer. The standardized extract of ARV showed inhibitory effects on the active MMP-2, pro MMP-2, pro MMP-9 depending on concentrations which was determined by zymography. However its inhibitory effect on pro MMP-9 was relatively weaker rather than active MMP-2, pro MMP-2. The standardized extract of ARV showed inhibitory effects in vitro on human fibrosarcoma cell (HT1080)'s invasion through Matrigel according to concentration. Conclusions : These results indicate that standardized extract of ARV has antimetastatic effect through inhibit again MMP-2, MMP-9. Also its inhibitory effect is more powerful on active MMP-2, pro MMP-2 than on active MMP-9, pro MMP-9. It is necessary to conduct further studies on other MMP families, TIMP, and each component of standardized extract of ARV.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.2
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• pp.505-509
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• 2012

Background: Matrix metalloproteinases (MMP) are proteolytic enzymes that are essentially involved in turnover of the extracellular matrix (ECM). The aim was to investigate the diagnostic value of MMP-7 and MMP-10 as tumor markers in pleural effusion (PE) and evaluate the value of combining MMP-7, MMP-10 and carcinoembryonic antigen (CEA) assays as diagnostic aids for malignant cells. Materials and Methods: A total of 179 patients with PE (87 malignant and 92 benign) were included in this study. The levels of MMP-7 and MMP-10 were measured using ELISA. Results: Values for MMP-7 and MMP-10 were significantly higher in malignant PE than those in benign PE (P<0.01). Among all variables evaluated, logistic regression found that MMP-7 and MMP-10 were significantly correlated with the presence of malignant disease (P<0.01). Analysis of receiver operating characteristics (ROC) curves showed that the area under the curve of MMP-10 (0.806) was significantly larger than that of MMP-7 (0.771) and CEA (0.789) (P<0.01). With parallel interpretation, the combination of MMP-10 and CEA achieved the higher sensitivity of 94.6%. The combination of MMP-7 and CEA in serial interpretation was able to boost the specificity to 95.7%. The combination of MMP-7, MMP-10 and CEA produced better sensitivity, specificity, PPV and NPV than MMP-7 and MMP-10 alone. Conclusion: MMP-7 and MMP-10 in PE may represent helpful adjuncts to conventional diagnostic tools in ruling out malignancy as a probable diagnosis, thus guiding the selection of patients who might benefit from further invasive procedures.

• Animal Bioscience
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• v.36 no.8
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• pp.1167-1179
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• 2023

Objective: Matrix metalloproteinases (MMPs) are a family of endoproteases produced by various tissues and cells and play important roles in angiogenesis, tissue repair, immune response, and endometrial remodeling. However, the expression and function of MMPs in the pig endometrium during the estrous cycle and pregnancy have not been fully elucidated. Thus, we determined the expression, localization, and regulation of MMP2, MMP8, MMP9, MMP12, and MMP13 in the endometrium throughout the estrous cycle and at the maternal-conceptus interface during pregnancy in pigs. Methods: Endometrial tissues during the estrous cycle and pregnancy and conceptus and chorioallantoic tissues during pregnancy were obtained and the expression of MMPs was analyzed. The effects of steroid hormones and cytokines on the expression of MMPs were determined in endometrial explant cultures. Results: Expression levels of MMP12 and MMP13 changed during the estrous cycle, while expression of MMP2, MMP9, MMP12, and MMP13 changed during pregnancy. Expression of MMP2, MMP8, and MMP13 mRNAs was cell type-specific at the maternal-conceptus interface. Gelatin zymography showed that enzymatically active MMP2 was present in endometrial tissues. In endometrial explant cultures, estradiol-17β induced the expression of MMP8 and MMP12, progesterone decreased the expression of MMP12, interleukin-1β increased the expression of MMP2, MMP8, MMP9, and MMP13, and interferon-γ increased the expression of MMP2. Conclusion: These results suggest that MMPs expressed in response to steroids and cytokines play an important role in the establishment and maintenance of pregnancy by regulating endometrial remodeling and processing bioactive molecules in pigs.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.28 no.3
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• pp.182-187
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• 2002

Matrix metalloproteinase(MMP) is the proteolytic enzyme of the extracellular matrix. MMPs play a role in the invasion and metastasis of malignant tumor, but it is not known whether the expression of MMPs in squamous cell carcinoma of the tongue is related to the prognostic factors of this tumor. In this study, 32 paraffin-embedded tumor specimens were examined immunohistochemically using monoclonal antibodies of MMP-2, MMP-3, MMP-10 and MMP-13. The possible relationships between the expressions of the MMPs and TNM staging, the differentiation of tumor cells, size of tumor mass and lymph node metastasis were anlaysed statistically. The results were as follows. 1. The expression of MMP-2 increased according to TNM staging (P<0.05) and lymph node metastasis (P<0.05) and the expression of MMP-2 was not affected by the differentiation of tumor cells or tumor size. 2. The expression of MMP-3 increased with increasing tumor size (P<0.05). However it was not related to TNM staging, the differentiation of tumor cells or lymph node metastasis. 3. The expression of MMP-10 was unrelated to TNM staging, differentiation of tumor cells, lymph node metastasis or tumor size. 4. The expression of MMP-13 increased as tumor size increased (P<0.05). However it was not related to TNM staging, the differentiation of tumor cells or lymph node metastasis. We concluded that the expression patterns of MMP-2, MMP-3, and MMP-13 may play a role in the diagnosis, treatment plan and prognostic evaluation of malignant tumors of the tongue.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.10
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• pp.4187-4192
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• 2014

Matrix metalloproteinase (MMP)-2 and MMP-9 are important proteases involved in invasion and metastasis of various tumors. Extra-gastrointestinal stromal tumors (EGISTs) are rare neoplasms. This study was performed to assess MMP-2 and MMP-9 expression in EGIST tissue samples for association with clinicopathological data from the patients. Twenty-one surgical EGIST tissue specimens were collected for analysis of MMP-2 and MMP-9 expression using immunohistochemistry. MMP-2 and MMP-9 proteins were expressed in all of the epithelial cell types of EGISTs, whereas they were only expressed in 75% of the spindle cell type, although there was no statistically significant difference (p>0.05). Expression of MMP-2 and MMP-9 proteins was associated with tumor size, mitotic rate, tumor necrosis, and distant metastasis (p<0.05). MMP-2 expression was linked with MMP-9 levels (p<0.05). However, there was no correlation between MMP-9 expression and age, sex, primary site, or cell morphology in any of these 21 EGIST patients (p>0.05). Moreover, expression of MMP-2 and MMP-9 proteins increased with the degree of EGIST risk. This study provided evidence of an association of MMP-2 and MMP-9 expression with advanced EGIST behavior.

• Environmental Analysis Health and Toxicology
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• v.24 no.1
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• pp.63-70
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• 2009

Naringenin, major one of the citrus flavonoids, have been identified that exert antioxidative, anticancer effects. The present study investigated the effects of naringenin on tumor invasion and matrix metalloproteinases(MMPs) activities. Naringenin inhibited cell invasion of HT-1080 fibrosarcoma cells in a dose-dependent manner. The activities of MMP-2 and MMP-9 were inhibited by naringenin as demonstrated by gelatin zymography assay. Furthermore, the amounts of MMP-2, MMP-9, and MT1-MMP mRNA were analyzed in the cells. MMP-2, MMP-9, and MT1-MMP mRNA expression were suppressed by naringenin with time and dose-dependent. These results demonstrate that anti-metastatic activities of naringenin resulted from blocking of invasion of the HT-1080 cells. Taken together, the results of this studies provide evidence that naringenin possess an anti-metastatic activity.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.4
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• pp.1327-1330
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• 2015

Background: Squamous cell carcinoma (SCC) is the most common cancer in the oral area. Matrix metalloproteinases (MMPs) and especially MMP-2 and MMP-9 are increased in malignancy and lymph node involvement in oral SCCs. We aimed to evaluate the serum levels of MMP-2 and MMP-9 in patients with oral SCC compared to normal subjects and their relation with clinicopathological findings. Materials and Methods: In this case control study, 20 patients with oral SCC and 20 healthy subjects were included and serum levels of MMP-2 and MMP-9 were compared between groups. Also, the correlation between these markers with clinicopathological findings including grade (T) and node (N) were evaluated. Results: Patients with oral SCC had significantly higher serum levels of MMP-2 (p=0.01) and MMP-9 (p<0.001) compared to healthy subjects. With increase in grade T, MMP-2 was significantly increased (p=0.001), but in the MMP-9 case this was not significant (p=0.27). The levels of MMP-2 (p=0.002) and MMP-9 (p=0.01) in cases with lymph node involvement and that of MMP-2 in subjects with smoking history (p=0.001) were significantly high. There was significantly positive correlation between MMP-2 with grade T tumor (r=0.598, p=0.005), lymph node involvement (r=0.737, p<0.001) and smoking (r=0.674, p=0.001) and also between MMP-9 and lymph node involvement (r=0.474, p=0.03). Conclusions: Both markers are significantly increased in oral SCC compared to healthy subjects. However, MMP-2 was better for evaluating lymph node involvement and tumor grade.

• Journal of Life Science
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• v.18 no.3
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• pp.422-425
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• 2008

Membrane-type 1 matrix metalloproteinase (MT1-MMP) is a membrane-associated zinc-dependent endoproteinase involved in extracellular matrix remodeling. MT1-MMP hydrolyzes ECM proteins like collagen and is involved in cancer cell migration and metastasis. Caveolins are integral membrane proteins and play a role in formation of caveolae, specialized membrane microdomains involved in clathrin-independent endocytosis. Recombinant MT1-MMP was transiently expressed in PANC-1 cells. Cells expressing recombinant MT1-MMP were able to hydrolyze collagen and migrate on collagen coated trans-well. Both subjacent collagen degradation and the cell migration conferred by recombinant MT1-MMP were inhibited by co-transfection of plasmids containing caveolin-1 cDNA. The results support that MT1-MMP is localized in lipid raft of the membrane and MT1-MMP activities in invasive cells could be inhibited by caveolin.

• BMB Reports
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• v.40 no.5
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• pp.825-831
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• 2007

Tumor cell invasion and metastasis are often associated with matrix metalloproteinases (MMPs), among which MMP-2 and MMP-9 are of central importance. We previously showed that H-Ras, but not N-Ras, induced invasion of MCF10A human breast epithelial cells in which the enhanced expression of MMP-2 was involved. MMP-2 is produced as a latent pro-MMP-2 (72 kDa) to be activated resulting the 62 kDa active MMP-2. The present study investigated if H-Ras and/or N-Ras induces pro-MMP-2 activation of MCF10A cells when cultured in two-dimensional gel of type I collagen. Type I collagen induced activation of pro-MMP-2 only in H-Ras MCF10A cells but not in N-Ras MCF10A cells. Induction of active MMP-2 by type I collagen was suppressed by blocking integrin ${\alpha}2$, indicating the involvement of integrin signaling in pro-MMP-2 activation. Membrane-type (MT)1-MMP and tissue inhibitor of metalloproteinase (TIMP)-2 were up-regulated by H-Ras but not by N-Ras in the type I collagen-coated gel, suggesting that H-Ras-specific up-regulation of MT1-MMP and TIMP-2 may lead to the activation of pro-MMP-2. Since acquisition of pro-MMP-2 activation can be associated with increased malignant progression, these results may help understanding the mechanisms for the cell surface matrix-degrading potential which will be crucial to the prognosis and therapy of breast cancer metastasis.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.32 no.4
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• pp.352-359
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• 2006

MMP-2 and MMP-9, type IV collagenases which degrade basement membrane, have been known to play important roles in invasion and metastasis of tumor cells, In addition, they seem to be involved in cell differentiation, apoptosis, angiogenesis and immunity, etc. We immunohistochemically examined epithelial and stromal expressions of MMP-2 and MMP-9 in irritation fibroma, oral leukoplakia, and oral squamous cell carcinoma (OSCC) and have some results as follows: 1. Irritation fibromas, oral leukoplakias and OSCCs mostly showed increased expression of MMP-2 and MMP-9 in the epithelium and connective tissue compared with normal mucosa. 2. There was a significant difference in the epithelial expression of MMP-2 and MMP-9 between irritation fibroma and oral leukoplakia. 3. There was a significant difference in the epithelial and stromal expression of MMP-2 and MMP-9 between irritation fibroma and OSCC. 4. There was a significant difference in the stromal expression of MMP-9 between oral leukoplakia and OSCC. We concluded that rritation fibroma, oral leukoplakia and OSCC have somewhat different characteristics of MMP-2 and MMP-9 expressions, which perhaps result from different pathogenesis.