• Journal of Yeungnam Medical Science
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• 제23권1호
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• pp.82-89
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• 2006

최근 여러 종양에서 단백분해효소의 분비와 암의 악성도에 대한 연구가 이루어져 왔으며, 이를 신세포암종 환자의 예후 측정인자로 사용하려는 시도가 진행되고 있다. 이에 저자들은 제 4형 collagenase 중 대표적인 MMP-9의 발현정도를 정상 신조직과 신세포암종 조직에서 비교하였고, 또 암의 침윤 및 전이정도와의 관계와 다른 임상적 인자들과의 상관성을 분석하여 암의 단계적 진행과정에서의 MMP-9의 발현변화에 대하여 조사하였다. 그 결과 정상 신 조직에 비해 신세포암종 조직에서 MMP-9의 발현이 증가되며 암의 크기가 크고 혈관침범이 있으며 병기가 높을수록 MMP-9의 발현이 증가됨을 관찰할 수 있었다. 이는 MMP-9 발현의 증가가 신세포암종의 발생과정 및 암의 후기 진행에 관여함을 시사하므로 향후 신세포암종의 예후척도로 사용되어 치료방침을 결정하는데 도움을 줄 수 있을 것으로 생각한다.

• Journal of Periodontal and Implant Science
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• 제43권1호
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• pp.24-29
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• 2013

Purpose: Matrix metalloproteinases (MMPs) are capable of degrading extracellular matrix, and they are inducible enzymes depending on an inflammatory environment such as periodontitis and bacterial infection in periodontal tissue. Gingival inflammation has been postulated to be correlated with the production of MMP-2 and MMP-9. The objective of this study was to quantify the expression and activity of MMP-9 and -2, and to determine the correlation between activity and expression of these MMPs in human gingival tissues with periodontitis. Methods: The gingival tissues of 13 patients were homogenized in $500{\mu}L$ of phosphate buffered saline with a protease inhibitor cocktail. The expression and activity of MMP-2 and -9 were measured by enzyme-linked immunosorbent assay and Western blot analysis, and quantified by a densitometer. For the correlation line, statistical analysis was performed using the Systat software package. Results: MMP-9 was highly expressed in all gingival tissue samples, whereas MMP-2 was underexpressed compared with MMP-9. MMP-9 activity increased together with the MMP-9 expression level, with a positive correlation (r=0.793, P=0.01). The correlation was not observed in MMP-2. Conclusions: The expression of MMP-2 and -9 might contribute to periodontal physiological and pathological processes, and the degree of MMP-9 expression and activity are predictive indicators relevant to the progression of periodontitis.

• Journal of Nutrition and Health
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• 제38권2호
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• pp.104-111
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• 2005

Tumor invasion is composed of four steps: cell adhesion to the extracellular matrix, degradation of the extracellular matrix components, tumor cell motility followed by cell detachment. Matrix metalloproteinases (MMPs) are important proteinases that associated with degradation of matrix component. Epigallocatechin gallate (EGCG) is a major polyphenotic constituent of green tea. In the study, we examined the anti-invasive and MMP activity suppression effects of EGCG in MDA-MB-231 human breast cancer cells. MDA-MB-23l human breast cancer cells were cultured with various concentrations 0 - 100 μM of EGCG. EGCG significantly inhibited the cell adhesion to the fibronectin. Cell motility through gelatin filter and invasion to Matrigel were inhibited dose-dependently by EGCG treatment. EGCG also inhibited the activities of MMP-2, -9 and the amount of MMP-9 (α = 0.05). Therefore, EGCG may contribute to the potential beneficial food component to prevent the invasion and metastasis in breast cancer. (Korean J Nutrition 38(2): 104～111, 2005)

• Asian Pacific Journal of Cancer Prevention
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• 제13권6호
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• pp.2437-2444
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• 2012

Tumor metastasis remains the principal cause of treatment failure and poor prognosis in patients with colorectal cancer. It is a multistage process which includes proteolysis, motility and migration of cells, proliferation in a new site, and neoangiogenesis. A crucial step in the process of intra- and extra-vasation is the activation of proteolytic enzymes capable of degrading the extracellular matrix (ECM). In this stage, urokinase plasminogen activator receptor (uPAR) and matrix metalloproteinases (MMPs) are necessary. Micrometastases need the presence of growth factor and vascular growth factor so that they can form macrometastasis. In addition, cell adhesion molecules (CAMs) and guanine nucleotide exchange factors (GEFs) play important roles in the progression of colorectal cancer and metastatic migration. Further elucidation of the mechanisms of how these molecules contribute will aid in the identification of diagnostic and prognostic markers as well as therapeutic targets for patients with colorectal metastasis.

• Preventive Nutrition and Food Science
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• 제22권3호
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• pp.184-190
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• 2017

Matrix metalloproteinases (MMPs) are endopeptidases that take significant roles in extracellular matrix degradation and therefore linked to several complications such as metastasis of cancer progression, oxidative stress, and hepatic fibrosis. Hizikia fusiformis, a brown algae, was reported to possess bioactivities, including but not limited to, antiviral, antimicrobial, and anti-inflammatory partly due to bioactive polysaccharide contents. In this study, the potential of H. fusiformis against cancer cell invasion was evaluated through the MMP inhibitory effect in HT1080 fibrosarcoma cells in vitro. H. fusiformis crude extract was fractionated with organic solvents, $H_2O$, n-BuOH, 85% aqueous MeOH, and n-hexane (n-Hex). The non-toxicity of the fractions was confirmed by MTT assay. All fractions inhibited the enzymatic activities of MMP-2 and MMP-9 according to the gelatin zymography assay. Cell migration was also significantly inhibited by the n-Hex fraction. In addition, both gene and protein expressions of MMP-2 and -9, and tissue inhibitor of MMPs (TIMPs) were evaluated by reverse transcription-polymerase chain reaction and Western blotting, respectively. The fractions suppressed the mRNA and protein levels of MMP-2, MMP-9 while elevating the TIMP-1 and TIMP-2, with the $H_2O$ fraction being the least effective while n-Hex fraction the most. Collectively, the n-Hex fraction from brown algae H. fusiformis could be a potential inhibitor of MMPs, suggesting the presence of various derivatives of polysaccharides in high amounts.

• KSBB Journal
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• 제16권3호
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• pp.237-240
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• 2001

본 연구에서는 keratinocytes 세포를 이용하여 VEGF가 세포의 증식, MMP-2 및 plasmin 분비에 미치는 영향을 조사하였다. 그 결과 VEGF는 keratinocytes의 세포증식을 약 2.5배 상승시켜 내피세포 뿐반 아니라 상피세포에서도 강력한 mitogen임을 확인하였으며 submaximal effect를 보이는 농도는 10 ng/mL이었다. VEGF의 농도 증가에 따른 MMP-2의 분비에 미치는 효과 역시 10 ng/mL에서 최대 효과를 나타냈으며 VEGF 처리 후 1시간만에 확인 가능한 MMP-2 밴드가 나타났다. 한편, MMP-2의 분비 증가와 함께 plasmin의 분비 증가가 수반되는지를 확인한 결과 VEGF를 첨가했을 때 약 3배 정도 plasmin의 분비량이 증가함을 알 수 었었다. 이러한 결과는 VEGF의 성장촉진 효과와 관련자어 볼 때 MMP-2와 plasmin이 keratinocytes 세포의 성장과 이동에 부분적으로 관여할 것임을 시사하고 있다.

• 한국수정란이식학회지
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• 제33권3호
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• pp.99-105
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• 2018

To determine the differences in the in-vitro ovum maturation process of bovine, we compared the expression of MMPs in these oocytes and cumulus cell throughout oocytes maturated. In an attempt to investigate the effect of MMP activation and inhibitors in total protein of cumulus cell and, oocytes during oocytes maturation, we examined and monitored the localization and expression of MMPs (MMP-2 and MMP-9), TIMPs (TIMP-2 and TIMP-3), as well as their expression profiles (Real-time PCR, Gelatin Zymography and ELISA). Our results that the bovine oocytes MMP-2 and MMP-9 level was significantly associated with the rate of maturity of oocytes (P<0.05). In cumulus cell, MMP-2 was highly expressed in all stages of the oocyte's maturation. The final oocytes maturation exhibited strong gelatinase activity. There was no significant correlation between cumulus cell MMP-9 and the maturation rate of oocytes. However, for the oocyte cytoplasm MMP-9 expression was significant correlation to the maturation oocytes. There was no significant correlation between cumulonimbus cells MMP-9 and oocyte maturation rates; however, for oocyte cytoplasm, MMP-9 expression was significantly correlated with mature oocyte. However, the TIMP-1 and TIMP-2 protein expression patterns are not correlated with the maturation rate of the oocyte. Our results suggest that MMP different expression pattern may regulate the morphological remodeling of oocyte's in the cumulus cell. Further, the MMP-2 expression has a strong relation with a higher maturation rate of the oocyte.

• 분석과학
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• 제28권6호
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• pp.361-369
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• 2015

골관절염에 대한 참당귀 추출분말 (AGE)의 치료효과를 검토하고자 토끼연골세포와 흰쥐의 monosodium iodoacetate (MIA)로 유발된 골관절염 부위에서 시료를 채취하여 MMPs의 발현에 대한 AGE의 억제 효능을 검토하였다. 고 농도의 AGE (50 μg/mL) 투여에서 세포독성은 관찰되지 않았으며 면역 및 염증반응과 관련된 여러 인자의 전사인자인 NF-κB 활성화를 효과적으로 억제시켰다. 토끼연골 세포에서 MMP-2와 MMP-9의 활성을 확인해본 결과 AGE는 MMP-9의 활성을 효과적으로 억제시키는 것을 확인하였다. AGE를 토끼연골세포에 처리하여 분석한 결과, 주요성분인 decursin과 decursinol angelate가 3.62±0.47 μg/mg protein와 2.14±0.36 μg/mg protein으로 검출되었다. 동물실험을 위하여, 골관절염은 MIA를 흰쥐 무릎관절에 처리하여 동물모델을 만들었으며, 매일 25, 50와 100 mg/kg의 AGE를 3주 동안 먹인 결과 흰쥐의 연골 조직에서 MMPs가 억제되는 것을 확인하였다. 연골조직으로부터 RT-PCR을 통해 collagen Type I, collagen Type II, aggrecan 및 MMPs (MMP-3, MMP-9, MMP-13)의 mRNA를 확인해본 결과 AGE는 collagen Type I, collagen Type II, aggrecan은 증가시키며 MMPs는 감소시키는 효과를 얻었다. 결론적으로 AGE는 MMPs 억제를 통하여 골관절염의 발생을 억제한다.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제27권4호
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• pp.314-320
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• 2001

Matrix metalloproteinases have long been viewed as ideal candidates for proteinases that enables tumor cells to permeated basement membrane defenses and invade surrounding tissue. There is growing evidence that the MMPs have an expanded role, as they are important for the creation and maintenance of a microenvironment that facilitates growth and angiogenesis of tumors at primary and metastatic sites. MT-MMPs are not secreted but instead remaining attached to cell surfaces. Although not all of the MT-MMPs are fully characterized, MT-MMPs have important role in localizing and activating secreted MMPs. The MMP genes are transcriptionally responsive to a wide variety of oncogene, growth factors, cytokine, and hormones. Currently, a number of MMP inhibitors are being developed and some have reached clinical trials as anti-metastatic or anti-cancer therapies. MT1-MMP is involved in the activation of proMMP-2. MT1-MMP is significant not only as a tumor marker but as a new target for chemotherapy against cancer. The purpose of this study was to evaluate the effects of protein kinase C inhibitor(genistein) on the proliferation of HT1080 and expression of MT1-MMP mRNA. Human fibrosarcoma cell line HT1080 was cultured and divided 2 groups. The experimental group was treated with $100{\mu}M$ genistein and incubated 12h, 24h for $[3^H]-thymidine$ uptake assay and northern hybridization individually. And the control group was treated with same amount of PBS for the above procedures. $[3^H]-thymidine$ incorporation was measured with ${\beta}$ ray detector. And RT-PCR and northern blotting for MT1-MMP mRNA was performed. The results were as follows 1. $[3^H]-thymidine$ uptake was reduced in experimental group with statistical significance. 2. MT1-MMP mRNA expression was significantly reduced in experimental group. These results showed that protein kinase C inhibitor (genistein) inhibited proliferation of HT1080 and almost completely blocked transcription of MT1-MMP mRNA. So, it is possible to use the protein kinase inhibitor (genistein) as anti-metastatic and anti-proliferative agent.

• 대한한의학회지
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• 제27권1호
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• pp.229-239
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• 2006

Objectives : Articular cartilage is a potential target for drugs designed to inhibit the activity of matrix metalloproteinases (MMPs) to stop or slow the destruction of the proteoglycan and collagen in the cartilage extracelluar matrix. The purpose of this study was to investigate the effects of KHBJs for cartilage-protective effect in human and rabbit articular cartilage explants. Methods : The cartilage-protective effects of KHBJ were evaluated by using glycosaminoglycan degradation assay, collagen degradation assay, colorimetric analysis of MMPs activity, and histological analysis in rabbit and human cartilage explants culture. Results : KHBJs significantly inhibited GAG and collagen release of rabbit and human cartilage explant in a concentration-dependent manner. Also, KHBJs inhibited MMP-3 and MMP-13 activities from IL-$1{\alpha}$-treated cartilage explants cultures. Histological analysis indicated that KHBJ004 reduced the degradation of the cartilage matrix compared with that of IL-$1{\alpha}$-treated cartilage explants. KHBJ004 had no harmful effect on chondrocytes viability or cartilage morphology in cartilage explants. Conclusions : These results indicate that KHBJs inhibits the degradation of proteoglycan and collagen through the downregulation of MMP-3 and MMP-13 activities without affecting the viability or morphology of IL-$1{\alpha}$-stimulated rabbit and human articular cartilage explants.