• Title/Summary/Keyword: matrix metalloproteinase-2

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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.

Effects of Citrus sunki Peel Extract on Matrix Metalloproteinase-1 Expression (진귤 과피 추출물의 MMP-1 발현조절 효과)

  • Han, Gu-Seul;Lee, Sun-Ryung
    • Journal of Life Science
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    • v.23 no.12
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    • pp.1553-1556
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    • 2013
  • Flavonoids are one of the major components found in the peels of citrus fruits. Present evidence has suggested that polymethoxyflavonoids, including nobiletin and tangeretin isolated from Citrus sunki, have many biological properties, such as anti-inflammatory, anti-oxidant, and anti-obesity capabilities. Here, we investigated the effect of Citrus sunki peel extract and its possible mechanisms on oxidative stress-induced MMP-1 expression, a major marker of skin photoaging. $H_2O_2$ induced MMP-1 expression in a dose- and time-dependent manner. Extract of Citrus sunki peel (1-25 ${\mu}g/ml$) dose-dependently decreased MMP-1 mRNA levels. When $H_2O_2$ was combined with Citrus sunki peel extract, the phosphorylation of ERK was further decreased compared to a single treatment with $H_2O_2$ alone. Moreover, U0216, an MEK inhibitor, markedly prevented the production of MMP-1. These data suggest that Citrus sunki peel extract has demonstrated protective activity against oxidative damage on MMP-1 expression, and ERK MAP kinase may be involved.

DIFFERENT EFFECTS OF QUERCETIN ON MATRIX METALLOPROTEINASES EXPRESSION IN EARLY AND LATE PASSAGE HUMAN FIBROBLASTS

  • Eum, Sung-Yong;Oh, Jang-Hee;Park, Jong-Min;Chung, An-Sik
    • Proceedings of the Korean Society of Toxicology Conference
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    • 2001.10a
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    • pp.158-158
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    • 2001
  • Bioflavonoids have been regarded as therapeutic agents for a wide range of disease including cancer. The increase of matrix metalloproteinases expression is a key event in several pathological conditions, e.g., dermal photocarcinogenesis, tumor initiation, invasion and metastasis. In this study, we investigated effects of quercetin, a major bioflavonoid in human diet, on matrix metalloproteinase (MMR)-1, MMP-2, MMP-3, MMP-9 mRNA expression during cellular aging in cultured human foreskin fibroblast. (omitted)

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Inhibitory Effects of Type IV Collagenase by Disulfiram (Disulfiram에 의한 type IV collagenase 저해효과)

  • Sin, Doo-Il;Park, Jae-Bok;Park, Kwan-Kyu;Cho, Chang-Ho;Oh, Hoon-Kyu;Choi, Chang-Hyuk;Cho, Hyun-Ji;Chang, Young-Chae
    • Journal of Life Science
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    • v.16 no.6
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    • pp.964-971
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    • 2006
  • The cancer cells, characterized by local invasion and distant metastasis, are very dependant on extracellular matrix. The expression of matrix metalloproteinases (MMPs) has been implicated in the invasion and metastasis of cancer cells. Among the human MMPs, matirx metalloproteinase-2 (MMP-2) and matrix metalloproteinse-9 (MMP-9) are key enzymes that degrade type IV collagen of the matrix. Here, we studied the effect of disulfiram, an anti-tumor compound, on the suppression of the tumor invasion and the activity of MMP-2, MMP-9 in human osteosarcoma cells (U2OS). Disulfiram had the type IV collagenase inhibitory activity, the effect of inhibition of gene and protein expression, and these inhibitions were responsible for blocking invasion through cell mediated and non-cell mediated pathways. In conclusion, disulfiram inhibited expression of MMP-2 and MMP-9, and regulated the invasion of U2OS, Caki-1 and Caski. These observations raise the possibility of clinical therapeutic applications for disulfiram used as a potential inhibitor of cancer invasion.

Influence of Smoking on Matrix Metalloproteinase-9 in the Gingival Crevicular Fluid (흡연이 치은열구액 내 Matrix Metalloproteinase-9에 미치는 영향)

  • Hwang, Soo-Jeong;Kim, Young-Kwon;Yang, Seong-Ju;Cho, Hyun-Jeong
    • Journal of dental hygiene science
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    • v.11 no.4
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    • pp.339-344
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    • 2011
  • Matrix metalloproteinase(MMP)-9 is considered important in tissue destruction in periodontitis. The aim of this study was to investigate the influence of smoking on MMP-9 in the gingival crevicular fluid(GCF). GCF samples in upper incisors area from 332 male subjects were collected after the informed consent. The dental examination included the assessment of oral hygiene, gingival inflammation and probing pocket depth. A quantitative assessment of MMP-9 levels in GCF was performed utilizing and immunological procedure. The mean MMP-9 concentrations found in GCF of smokers(30.86 ng/ml) and quit-smokers(29.82 ng/ml) differed from non-smokers(11.33 ng/ml), adjusted by age, gingival index and Community periodontal index(p<0.001). Smoking seems to influence MMP-9 in GCF regardless of gingival inflammation and age. It means smoking can destruct the periodontal tissue for itself.

Possible Role of Matrix Metalloproteinase in Osteolytic Intracranial Meningiomas

  • Moon, Hyung-Sik;Jung, Shin;Jung, Tae-Young;Cao, Van Thang;Moon, Kyung-Sub;Kim, In-Young
    • Journal of Korean Neurosurgical Society
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    • v.47 no.1
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    • pp.11-16
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    • 2010
  • Objective: Abnormalities of the bone are frequently encountered in patients with meningioma, and hyperostosis and endostosis are common bone alterations in these tumors. Extensive bony destruction is very unusual in patients with meningioma. We report six cases of intracranial meningioma associated with an osteolytic lesion of the skull and discuss the underlying mechanisms that may be responsible for bone destruction in patients with meningioma. Methods: Six patients were classified into three groups, severe, moderate and mild, according to the degree of osteolytic bony destruction. The tumor was classified as intracranial or extracranial, depending on its location. We investigated the potential role of matrix metalloproteinase (MMP) in meningioma-associated osteolysis. The levels of MMP expression were determined by gelatin zymography, reverse transcription-quantitative PCR analysis (RT-PCR) and immunohistochemical analysis. Results: Complete surgical removal of the lesion was performed in each patient. Histological examination revealed benign meningioma in four cases, and two cases of atypical meningioma. Patients did not have a poor prognosis except one case of recurred atypical meningioma. Gelatin zymography and RT-PCR detected high levels of MMP-2 in almost all extracranial masses in comparison with the intracranial masses and MMP9 in two. There was no difference in the severity of bone destruction. Immunohistochemical analysis revealed MMP-2 expression in the vicinity of the bone destruction, and a few MMP-9-positive stainings were observed. Conclusion: Osteolysis of the skull in patients with meningiomas might not be indicative of malignant pathological features and poor prognosis. Invasion to the extracranial portion and osteolysis might be associated with MMP-2 expression in meningioma.

Genistein Suppression of Matrix Metalloproteinase 2 (MMP-2) and Vascular Endothelial Growth Factor (VEGF) Expression in Mesenchymal Stem Cell Like Cells Isolated from High and Low Grade Gliomas

  • Yazdani, Yasaman;Rad, Mohammad Reza Sharifi;Taghipour, Mousa;Chenari, Nooshafarin;Ghaderi, Abbas;Razmkhah, Mahboobeh
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.12
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    • pp.5303-5307
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    • 2016
  • Objective: Brain tumors cause great mortality and morbidity worldwide, and success rates with surgical treatment remain very low. Several recent studies have focused on introduction of novel effective medical therapeutic approaches. Genistein is a member of the isoflavonoid family which has proved to exert anticancer effects. Here we assessed the effects of genistein on the expression of MMP-2 and VEGF in low and high grade gliomas in vitro. Materials and Methods: High and low grade glioma tumor tissue samples were obtained from a total of 16 patients, washed with PBS, cut into small pieces, digested with collagenase type I and cultured in DMEM containing 10% FBS. When cells reached passage 3, they were exposed to genistein and MMP-2 and VEGF gene transcripts were determined by quantitative real time PCR (qRT-PCR). Results: Expression of MMP-2 demonstrated 580-fold reduction in expression in low grade glioma cells post treatment with genistein compared to untreated cells (P value= 0.05). In cells derived from high grade lesions, expression of MMP-2 was 2-fold lower than in controls (P value> 0.05). Genistein caused a 4.7-fold reduction in VEGF transcript in high grade glioma cells (P value> 0.05) but no effects were evident in low grade glioma cells. Conclusion. Based on the data of the present study, low grade glioma cells appear much more sensitive to genistein and this isoflavone might offer an appropriate therapeutic intervention in these patients. Further investigation of this possibility is clearly warranted.

Korean Red Ginseng suppresses bisphenol A-induced expression of cyclooxygenase-2 and cellular migration of A549 human lung cancer cell through inhibition of reactive oxygen species

  • Song, Heewon;Lee, Yong Yook;Park, Joonwoo;Lee, YoungJoo
    • Journal of Ginseng Research
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    • v.45 no.1
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    • pp.119-125
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    • 2021
  • Background: Korean Red Ginseng (KRG) is a natural product with antiinflammatory and anticarcinogenic effects. We have previously reported that the endocrine-disrupting compound bisphenol A (BPA)-induced cyclooxygenase-2 (COX-2) via nuclear translocation of nuclear factor-kappa B (NF-κB) and activation of mitogen-activated protein kinase and promoted the migration of A549. Here, in this study, we assessed the protective effect of KRG on the BPA-induced reactive oxygen species (ROS) and expression of COX-2 and matrix metalloproteinase-9 (MMP-9) in A549 cells. Methods: The effects of KRG on the upregulation of ROS production and COX-2 and MMP-9 expression by BPA were evaluated by fluorescence-activated cell sorting (FACs) analysis, quantitative reverse transcription polymerase chain reaction, and western blotting. Antimigration ability by KRG was evaluated by migration assay in A549 cells. Results: KRG significantly suppressed the BPA-induced COX-2, the activity of NF-κB, the production of ROS, and the migration of A549 cells. These effects led to the downregulation of the expression of MMP-9. Conclusions: Overall, our results suggest that KRG exerts an antiinflammatory effect on BPA-treated A549 cells via the suppression of ROS and downregulation of NF-κB activation and COX-2 expression which leads to a decrease in cellular migration and MMP-9 expression. These results provide a new possible therapeutic application of KRG to protect BPA-induced possible inflammatory disorders.

Inhibitory Effect of Artemisiae Annuae Herba Extracts on Melanin Synthesis, Tyrosinase Activities and Production Levels of Tyrosinase, MMP-1 and MMP-9 in SK-MEL-2 Cells (SK-MEL-2 세포에서 청호(靑蒿) 추출물의 Melanin 생성, Tyrosinase 활성과 생성, MMP-1 및 MMP-9 생성 억제 효과)

  • Lee, Eun-Kyu;Kim, Soo-Hyeon;Park, Kyung-Mi;Yang, Seung-Jeong;Cho, Seong-Hee
    • The Journal of Korean Obstetrics and Gynecology
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    • v.30 no.2
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    • pp.37-48
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    • 2017
  • Objectives: Artemisiae Annuae Herba is the dried aerial part of Artemisia annua L. (AAL). In Oriental medicine, Artemisiae Annuae Herba (AAH) is traditionally used to treat fever. AAH clears summerheat or damp-Heat, clears deficiency fevers, cools the blood and stops bleeding, stops malarial disorders and relieves heat, clears liver heat and brightens the eyes. Recently, there were many studies about effects of AAH on anti-oxidative, anti-inflammatory, anti-cancer, hair growth and plasma lipid composition. So, we expected AAH has an availability that can effect on skin whitening and elasticity. Methods: The present study was designed to investigate the effects of AAH on skin whitening and elasticity in SK-MEL-2 cells. In this experiment, the effects of AAH on proliferation rates, melanin synthesis, tyrosinase activities and production levels of tyrosinase, MMP-1 and MMP-9 in vitro were examined. Results: AAH did not affect viability of SK-MEL-2 cells and inhibited melanin synthesis induced by ${\alpha}$-Melanocyte-stimulating hormone (${\alpha}$-MSH) significantly. In addition, AAH also inhibited tyrosinase activity and lowered tyrosinase level in SK-MEL-2 cells. Finally, AAH inhibited productions of Matrix metalloproteinase-1 (MMP-1) and Matrix metalloproteinase-9 (MMP-9). Conclusions: These data suggest that AAH can be used to treat patients with skin diseases such as freckled face and also used as skin whitening agent.

Expression of RECK and MMPs in Hepatoblastoma and Neuroblastoma and Comparative Analysis on the Tumor Metastasis

  • Xu, Meng;Wang, Hai-Feng;Zhang, Huan-Zhi
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.9
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    • pp.4007-4011
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    • 2015
  • Objective: To explore the expression of RECK and relevant matrix metalloproteinases (MMPs) in hepatoblastoma (HB) and neuroblastoma (NB) and their clinical significance in the tumor metastasis. Materials and Methods: Forty-five wax-stone samples of HB and 43 wax-stone samples of NB removed by surgical resection and confirmed by pathology in Linyi Yishui Central Hospital were selected. According to presence and absence of metastasis, both NB and HB samples were divided into metastatic group and non-metastatic group, namely NB metastatic group (n=28), NB non-metastatic group (n=15), HB metastatic group (n=15) and HB non-metastatic group (n=30). The expression of RECK, membrane type-1 matrix metalloproteinase (MT1-MMP) in HB tissue and RECK, MMP-14 in NB tissue was detected using immunohistochemical method, and the correlation between RECK and MT1-MMP, MMP-14 was analyzed. Results: The metastatic rate of NB was dramatically higher than that of HB, with statistical significance (P=0.003). The positive rate of RECK expression in NB group (30.2%) was slightly lower than in HB group (40.0%), but no significant difference was presented (P=0.338). The positive rate of MMPs expression in NB metastatic group was evidently higher than in HB metastatic group (P=0.024). The results of Spearman correlation analysis revealed that the expression of RECK in HB and NB tissues had a significantly-negative correlation with MT1-MMP and MMP-14, respectively (r=-0.499, P=0.012; r=-0.636, P=0.000). Conclusions: In HB and NB tissues, RECK is expressed lowly, while relevant MMPs highly, and RECK inhibits the tumor invasion and metastasis through negative regulation of relevant MMPs.