• Title, Summary, Keyword: MMP

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Effect of Allergen Removed Rhus Verniciflua Extract on Inhibition of Tumor Metastasis (알러젠 제거 옻나무 추출물이 종양 전이 억제에 미치는 영향)

  • Park, Jae-Hyun;Moon, Goo
    • 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.

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Application of MMP-7 and MMP-10 in Assisting the Diagnosis of Malignant Pleural Effusion

  • Cheng, Daye;Liang, Bin;Li, Yun-Hui
    • 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.

THE EXPRESSION OF MMP-2, MMP-3, MMP-10, MMP-13 IN SQUAMOUS CELL CARCINOMA OF THE TONGUE (혀의 편평상피세포암에서 MMP-2, MMP-3, MMP-10, MMP-13의 발현 양상)

  • Yun, Kyoung-In;Pyo, Sung-Woon;Kim, Young-Sill;Lee, Cheol-Won
    • 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.

Upregulation of MMP is Mediated by MEK1 Activation During Differentiation of Monocyte into Macrophage

  • Lim, Jae-Won;Cho, Yoon-Jung;Lee, Dong-Hyun;Jung, Byung-Chul;Kang, Han-Sol;Kim, Tack-Joong;Rhee, Ki-Jong;Kim, Tae-Ue;Kim, Yoon-Suk
    • Biomedical Science Letters
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    • v.18 no.2
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    • pp.104-111
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    • 2012
  • Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases which degrade extracellular matrix (ECM) during embryogenesis, wound healing, and tissue remodeling. Dysregulation of MMP activity is also associated with various pathological inflammatory conditions. In this study, we examined the expression pattern of MMPs during PMA-induced differentiation of THP-1 monocytic cells into macrophages. We found that MMP1, MMP8, MMP3, MMP10, MMP12, MMP19, MMP9, and MMP7 were upregulated during differentiation whereas MMP2 remained unchanged. Expression of MMPs increased in a time-dependent manner; MMP1, MMP8, MMP3, MMP10, and MMP12 increased beginning at 60 hr post PMA treatment whereas MMP19, MMP9, and MMP7 increased beginning at 24 hr post PMA treatment. To identify signal transduction pathways involved in PMA-induced upregulation of MMPs, we treated PMA-differentiated THP-1 cells with specific inhibitors for PKC, MEK1, NF-${\kappa}B$, PI3K, p38 MAPK and PLC. We found that inhibition of the MEK1 pathway blocked PMA-induced upregulation of all MMPs to varying degrees except for MMP-2. In addition, expression of select MMPs was inhibited by PI3K, p38 MAPK and PLC inhibitors. In conclusion, we show that of the MMPs examined, most MMPs were up-regulated during differentiation of monocyte into macrophage via the MEK1 pathway. These results provide basic information for studying MMPs expression during macrophage differentiation.

Association of Matrix Metalloproteinase (MMP)-2 and -9 Expression with Extra-gastrointestinal Stromal Tumor Metastasis

  • Wang, Chao;Ma, Hong-Xi;Jin, Mei-Shan;Zou, Ya-Bin;Teng, Yong-Liang;Tian, Zhuang;Wang, Hai-Ying;Wang, Yin-Ping;Duan, Xiu-Mei
    • 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.

Inhibitory Effect of Naringenin on MMP-2, -9 Activity and Expression in HT-1080 Cells (HT1080 세포주에서 naringenin의 MMP-2, -9 효소 활성 및 발현 억제 효과)

  • Chae, Soo-Chul
    • Environmental 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.

Caveolin-1 inhibits membrane-type 1 matrix metalloproteinase activity

  • Kim, Hye-Nan;Chung, Hye-Shin
    • BMB Reports
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    • v.41 no.12
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    • pp.858-862
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    • 2008
  • Membrane-type 1 matrix metalloproteinase (MT1-MMP) is a zinc-dependent proteinase found in cholesterol-rich lipid rafts on the plasma membrane. MT1-MMP hydrolyzes extracellular matrix (ECM) proteins, activates pro-matrix metalloproteinase-2 (proMMP-2) and plays an important role in ECM remodeling, cancer cell migration and metastasis. The role of caveolin-1, an integral protein of caveolae, in the activation of MT1-MMP remains largely unknown. Here, we show that the expression of caveolin-1 attenuates the activation of proMMP-2, reduces proteolytic cleavage of ECM and inhibits cell migration. We utilized the cytoplasmic tail domain deletion (${\Delta}CT$) or the E240A mutant of MT1-MMP. Co-expression of caveolin-1 with the wild-type or the ${\Delta}CT$ MT1-MMP decreased the proMMP-2 activation and inhibited collagen degradation and cell migration. Caveolin-1 had no effect on the catalytically inert E240A MT1-MMP. Our findings suggest that caveolin-1 is essential in the down-regulation of MT1-MMP activity by promoting internalization from the cell surface.

Serum Levels of MMP9 and MMP2 in Patients with Oral Squamous Cell Carcinoma

  • Lotfi, Alireza;Mohammadi, Ghodrat;Tavassoli, Atena;mousaviagdas, Mehrnoosh;Chavoshi, Hadi;Saniee, Lale
    • 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.

Inhibition of Invasion and Capillary-like Tube Formation by Retrohydroxamate-based MMP Inhibitors

  • Choi, Seung-Su;Ji, Ae-Ri;Yu, Seung-Woo;Cho, Bong-Hwan;Park, Jung-Dae;Park, Jun-Hyoung;Lee, Hyun-Soo;Ryu, Seong-Eon;Kim, Dong-Han;Kang, Jae-Hoon;Lee, Seung-Taek
    • Bulletin of the Korean Chemical Society
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    • v.32 no.6
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    • pp.2032-2038
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    • 2011
  • Matrix metalloproteinases (MMPs), a family of zinc-containing endopeptidases, participate in many normal processes such as embryonic development and wound repair, and in many pathological situations such as cancer, atherosclerosis, and arthritis. Peptidomimetic MMP inhibitors were designed and synthesized with N-formylhydroxylamine (retrohydroxamate) as a zinc-binding group and various side chains on the ${\alpha}$, P1', and P2' positions. Using in vitro MMP assays with purified MMPs (MMP-1, MMP-2, MMP-3, MMP-9, and MMP-14) and fluorogenic peptide substrates, it was found that compounds 2d and 2g selectively inhibit gelatinases (MMP-2 and MMP-9) and interstitial collagenase (MMP-1). They also inhibited the chemo-invasion of fibrosarcoma HT-1080 cells and tube formation of human umbilical vascular endothelial cells in a dose-dependent manner. Our results suggest that retrohydroxamate-based MMP inhibitors, especially compounds 2d and 2g, have the potential to be used as therapeutic drugs for cancer and other MMP-related diseases.

Activities of Recombinant MT1-MMP Expressed in PANC-1 Cells. (PANC-1세포에서 발현된 재조합 MT1-MMP의 효소 활성)

  • Kim, Hye-Nan;Chung, Hye-Shin
    • 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.