• Asian Pacific Journal of Cancer Prevention
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• 제13권2호
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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.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제28권3호
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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.

• Biomolecules & Therapeutics
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• 제10권4호
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• pp.240-245
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• 2002

Cancer metastasis represents the most important cause of cancer death and antitumor agents that may inhibit this process have been extensively pursued. Invasion and metastasis of malignantly transformed cells involve degradation of the extracellular matrix (ECM) components by matrix metalloproteinases (MMP), especially MMP-2 and -9. We previously showed that H-ras-induced invasive phenotype may involve MMP-2, rather than MMP-9, in MCF10A cells. In the present study, we investigated the chemopreventive effect of Aster, a widely used culinary vegetable in Korea. We screened twelve extracts from three Aster species (Aster scaber, Aster oharai and Aster glehni) for the inhibitory effect on MMP activities of H-ras MCF10A human breast epithelial cells. All of the extracts tested in this study efficiently inhibited the gelatinolytic activities of MMP-2 and MMP-9. A more prominent inhibition was observed in MMP-2 activity compared to MMP-9. Out of twelve extracts, eight extracts showed>90％ inhibition of MMP-2 activity in H-ras MCF10A cells while only one extract showed>90％ inhibition of MMP-9 activity. We selected three extracts (AO-3, AG-3 and AS-EA) for further studies since they exerted a marked inhibition in the ratio of MMP-2 to MMP-9. Treatment with AO-3, AG-3 and AS-EA in H-ras MCF10A cells caused a significant inhibition of invasive phenotype and migration, proving a chemopreventive potential of these extracts. Taken together, our results demonstrate that extracts of Aster effectively inhibit invasion and migration of highly malignant human breast cells, possibly via downregulation of MMP-2 and MMP-9.

• BMB Reports
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• 제40권5호
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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.

• Asian Pacific Journal of Cancer Prevention
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• 제15권10호
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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.

• Animal Bioscience
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• 제36권8호
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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.

• 생명과학회지
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• 제18권3호
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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.

• 생명과학회지
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• 제26권5호
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• pp.584-591
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• 2016

삼백초는 항산화 활성을 갖는 플라보노이드 화합물을 포함하고 있는 여러해살이 식물로 알려져 있다. 본 연구에서는 삼백초 물 추출물과 유기용매 분획물의 항산화 활성, 항염증 활성 및 PMA에 의해 유도된 MMP-2 및 MMP-9활성 억제 효과를 조사하였다. 시료들은 삼백초 물 추출을 헥산(hexane), 클로로포름(CHCl₃), 에틸 아세테이트(Ethyl acetate), 부탄올(butanol) 및 물(water)과 같은 용매로 분획화하여 사용하였고, 물 분획물의 수득율이 9.25%로 가장 높았다. 항산화 활성은 DPPH assay, 세포 생존율 측정은 MTS assay, 항염증 활성은 마우스 대식세포 Raw 264.7세포에서NO 생성 그리고 MMP-2 및 MMP-9의 mRNA 발현 및 단백질 활성 억제는 인간구강편평세포암종 YD-10B 세포에서 RT-PCR과 zymography방법을 통해 측정하였다. 본 연구의 결과에 의하면 MMP-2/-9 활성은 PMA에 의해 YD-10B세포에서 증가하였다. PMA 처리된 YD-10B 세포에서, 에틸 아세테이트 분획물이 증가된 MMP-2/-9의 mRNA 발현 및 단백질 활성을 유의하게 억제하였다. 그리고 항산화 활성도 에틸아세트 분획물이 73.38%의 가장 높게 나타났다. 또한 세포 독성을 나타내지 않는 농도에서, 에틸아세트 분획물이 Raw 264.7세포에서 농도 의존적으로 유의하게 항염증 활성을 보였다. 그러므로 본 연구에서는 삼백초 물 추출의 에틸아세트 분획물이 구강암의 암 침윤을 억제할 수 있는 효과적인 암 예방 및 치료를 위한 항암제로서의 가능성을 암시하고 있다.

• Restorative Dentistry and Endodontics
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• 제30권5호
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• pp.372-384
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• 2005

이 연구에서는 Prevotella nigrescens (P. nigrescens)의 lipopolysaccharide (LPS)로 자극한 치주인대 섬유아세포에서 matrix metalloproteinase (MMP)와 tissue inhibitor of metalloproteinase (TIMP)의 생성 양상과, LPS를 수산화칼슘으로 처리했을 때의 영향을 평가하였다. P. nigrescens에서 추출, 정제한 여러 농도의 LPS와 수산화칼슘으로 처리한 LPS로 치주인대 섬유아세포를 자극하여, Immunoprecipitation법으로 MMP-1, -2, TIMP-1의 단백질 생성 양상을, real-time polymerase chain reaction법으로 MMP-1의 mRNA 발현 양상을 분석하였다. 이 연구의 결과는 아래와 같다. 1. MMP-1은 단백질과 유전자 수준 모두 자극 시간과 비례하여 증가하여 48시간에 최대값을 보였다. 2. MMP-2단백질 생성은 1, 10 mg/ml에서 자극 시간과 비례하여 증가하였다. 3. TIMP-1 단백질 생성은 24시간까지 증가하다가 48시간에 감소하였고, 0.1과 1 ${\mg}g/ml$에서 증가하였으나 10 ${\mu}g/ml$ 에서 억제되었다. 4. P. nigrescens의 LPS를 수산화칼슘으로 처리시 MMP-1의 mRNA 발현은 현저하게 감소하였다.

• Biomolecules & Therapeutics
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• 제17권3호
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• pp.288-292
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• 2009

Interactions between tumor cells and the extracellular matrix (ECM) strongly influence tumor development, affecting cell survival, proliferation and migration. Fibronectin, a major component of ECM, has been shown to interact with integrins especially the ${\alpha}5{\beta}1$ integrin. Cell invasion and metastasis are often associated with matrix metalloproteinases (MMPs) which are capable of digesting the different components of the ECM and basement membrane. MMP-2 is produced as a latent pro-MMP-2 (72 kDa) to be activated, resulting the 62 kDa active MMP-2. In this study, we investigated the effect of fibronectin on activation of pro-MMP-2 and the cellular invasiveness in H-Ras-transformed MCF10A human breast epithelial cells. Here we show that fibronectin induces activation of pro-MMP-2 and up-regulation of MT1-MMP and TIMP-2 in H-Ras MCF10A cells. These results demonstrate that H-Ras MCF10A cells secrete high levels of active MMP-2 when cultured with fibronectin, suggesting a possible interaction between the ECM network and H-Ras MCF10A cells to generate active MMP-2 which is important for proteolysis and ECM remodeling. Invasive and migratory abilities of H-Ras MCF10A cells were enhanced by fibronectin. Fibronectin up-regulated the expression of ${\beta}1$ integrin which may play a role in cellular responses exerted by fibronectin. Since acquisition of pro-MMP-2 activation can be associated with increased malignant progression, this study provides a mechanism for the cell surface-matrix degrading effect of fibronectin which will be crucial to breast cell invasion and migration.