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良性黑色素细胞痣成熟过程中膜型基质金属蛋白酶-1(mt1-mmp)的作用

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世界核心医学期刊文摘（皮肤病学分册） 2006年第5期2卷 58-58页

作者： Pérez L.J. Peas P.F. AtienzarM. Garca-Dez A. 任建文 Av Espaa 25 Albacete 02002 Spain

Background: Metalloproteinases (mmps) are proteins involved in extracellular matrix breakdown and have been implicated in stages of migration and metastasis. mt1-mmp is an mmp anchored to the cell membrane. During maturation, melanocytic nevi penetrate the extracellular matrix and express mmps. Methods: We studied 10 junctional, 10 compound, and 10 intradermal nevi diagnosed by clinical and histological studies and by performing immunohistochemical study to assess mt1-mmp activity. Results: We found evidence of mt1-mmp expression in melanocytic nevus cells, particularly around the entire border of cell nests. Expression was more intense in junctional nevi and gradually decreased with acquisition of intradermal component and became nonexistent in nevi in the deep dermis. Conclusions: mt1-mmp is expressed in the membrane of nevus cells, with expression greater in nest cells in contact with the extracellular matrix. The intensity of expression correlated inversely with the maturation phase of the nevus, being very high in junctional nevi and low in intradermal nevi.

关键词：黑色素细胞 mt1-mmp 混合痣皮内痣交界痣细胞外基质真皮深层免疫组化法金属蛋白酶低

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大小肝癌中相关因子的表达差异及其意义

中国肿瘤临床 2006年第2期33卷 77-79页

作者：何萍张雁瑞车丽洪吴惠茜赵国强薛玲中山大学附属第一医院病理科

目的:比较影响大、小肝癌生物学行为差异的相关因素,并探讨其可能的机制。方法:采用免疫组化方法检测nm23-H1、c-Met、mt1-mmp(membrane-type1matrixmetalloproteinase)、Ki-67蛋白在53例大肝癌(瘤体直径>3cm)及40例小肝癌(单肿瘤结节,... 详细信息

目的:比较影响大、小肝癌生物学行为差异的相关因素,并探讨其可能的机制。方法:采用免疫组化方法检测nm23-H1、c-Met、mt1-mmp(membrane-type1matrixmetalloproteinase)、Ki-67蛋白在53例大肝癌(瘤体直径>3cm)及40例小肝癌(单肿瘤结节,瘤体直径≤3cm)中的表达,并分析其与肝癌临床病理因子的关系。结果:nm23-H1、c-Met、mt1-mmp蛋白在大、小肝癌组织中的表达差异显著(分别为P=0.005、P=0.008和P=0.007);nm23-H1蛋白表达与肿瘤远处转移之间呈负相关关系(P=0.041);c-Met、mt1-mmp蛋白表达与肿瘤包膜浸润、远处转移之间均呈正相关关系(P1、c-Met、mt1-mmp蛋白发生改变,是促使其生物学行为较小肝癌更为恶性的重要因素。

关键词：肝细胞癌转移 nm23-H1 c-Met mt1-mmp

非小细胞性肺癌中P-gp表达与CD147、mmps表达的关系

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复旦学报（医学版） 2005年第4期32卷 379-382,F002页

作者：董敏周仲文赵仲华张秀荣许祖德复旦大学上海医学院病理学系上海200032

目的研究肿瘤细胞自然状态下耐药时,肿瘤细胞多药耐药与转移的关系。方法选取112例未经化疗的非小细胞性肺癌手术切除标本,用免疫组织化学染色观察P-gp、CD147、mmp-1、mt1-mmp的蛋白表达,分析各指标之间的关系。结果人肺癌组织中P-gp... 详细信息

目的研究肿瘤细胞自然状态下耐药时,肿瘤细胞多药耐药与转移的关系。方法选取112例未经化疗的非小细胞性肺癌手术切除标本,用免疫组织化学染色观察P-gp、CD147、mmp-1、mt1-mmp的蛋白表达,分析各指标之间的关系。结果人肺癌组织中P-gp的表达与CD147、mmp-1、mt1-mmp具有明显的一致性,CD147、mmp-1、mt1-mmp在腺癌中表达高于鳞癌,且与淋巴结转移相关。结论非小细胞性肺癌自然状态下耐药时,P-gp与CD147、mmps等肿瘤浸润、转移相关蛋白的表达之间可能存在着共同的调节机制。CD147对mmps的调节,可能与多药耐药肿瘤的浸润、转移特性有关。

关键词：非小细胞性肺癌 CD147 P-gp表达 mmps表达 mt1-mmp mmp-1 细胞多药耐药手术切除标本免疫组织化学转移相关蛋白自然状态淋巴结转移肿瘤细胞染色观察蛋白表达肺癌组织肿瘤浸润调节机制转移特性一致性

1,25-二羟维生素D_3对人成骨细胞基质金属蛋白酶及其抑制因子的作用

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中华内科杂志 2005年第2期44卷 125-128页

作者：郭丽娟罗湘杭谢辉周后德廖二元中南大学湘雅二医院代谢内分泌研究所长沙410011

目的研究1,25-二羟维生素D3 [1α,25(OH)2D3]对人成骨细胞基质金属蛋白酶(mmp)-1、mmp-2、膜型基质金属蛋白酶-1(mt1-mmp)、基质金属蛋白酶抑制因子-1(TIMP-1)的影响,探讨1α,25(OH)2D3调节骨代谢作用机制. 方法人成骨细胞用1α,25(OH)... 详细信息

目的研究1,25-二羟维生素D3 [1α,25(OH)2D3]对人成骨细胞基质金属蛋白酶(mmp)-1、mmp-2、膜型基质金属蛋白酶-1(mt1-mmp)、基质金属蛋白酶抑制因子-1(TIMP-1)的影响,探讨1α,25(OH)2D3调节骨代谢作用机制. 方法人成骨细胞用1α,25(OH)2D3干预.Western杂交检测mt1-mmp蛋白质表达.mmp-1、mmp-2、TIMP-1的分泌及mmp-2的活性用ELISA检测. Northern杂交检测维生素 D 受体、 mt1-mmp mRNA表达. 结果 1α,25(OH)2D3对人成骨细胞mmp-1、mmp-2、TIMP-1表达无影响, 10-10～10-8 mol/L 1α,25(OH)2D3干预诱导成骨细胞 mt1-mmp表达呈剂量依赖性(P值均mmp-2激活呈剂量依赖性[mmp-2活性分别为(42.3 ± 8.6)、(64.4 ± 11.4)、(93.5 ± 9.9)μg/L, P值均mt1-mmp在骨吸收过程中起着关键作用,1α,25(OH)2D3可通过诱导成骨细胞mt1-mmp表达刺激骨吸收.

关键词：细胞基质金属蛋白酶 25-二羟维生素D3 mt1-mmp 基质金属蛋白酶抑制因子膜型基质金属蛋白酶 mmp-2 Northern TIMP-1表达 Western ELISA检测人成骨细胞 mmp-1 剂量依赖性维生素D受体 mRNA表达杂交检测蛋白质表达 mol/L

Integrin Alpha-V Beta-3-Matrix Metalloproteinase-2 (mmp-2), Cross-Talk

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Journal of Cancer Therapy 2015年第9期6卷 793-802页

作者： Hrishikesh Sil Amitava Chatterjee Department of Receptor Biology & Tumor Metastasis Chittaranjan National Cancer Institute Kolkata India Ramakrishna Mission Vivekananda University (IRDM) Narendrapur Kolkata India

The present study aimed to detect comparative expression of integrin αVβ3 and its involvement in expression and activation of matrix metalloproteinase-2 (mmp-2) in 25 malignant human breast tumor and adjacent normal breast tissues from different clinical TNM stages (DCIS to T4) of the disease and possible involvement of known regulating parameters of mmp-2 like TIMP-2, mt1-mmp and EMPRIN. Integrin αVβ3 was highly expressed in tumors than adjacent normal breast tissues. Pro-mmp-2(72-KD) was mainly expressed in adjacent normal tissues compared to tumors. The mature forms of mmp-2 (68 KD and 64 KD) were found only in tumors. Appreciable expression of TIMP-2 and induction of mt1-mmp and EMPRIN in T2-T4 stages suggested their possible role in mmp-2 activation. Over expression Integrin αVβ3 in tumors than adjacent normal breast tissues was an indication of cancer progression with involvement of integrin signaling. We conclude that, the co-precipitation of mmp-2 with αvβ3 by anti-αv antibody is a strong indication that integrin αvβ3 is a surface receptor for mmp-2 and αvβ3-mmp-2 complex on the surface of tumor cells may play a very important role in determining the invasive property and malignant behavior of tumor tissues. The positive expression of endogenous inhibitor of mmp-2, TIMP-2 may have an appreciable role in activation of this protease and risk of malignancy in advanced stage of the disease. The enhanced expression of mt1-mmp and EMPRIN suggested a role for these factors in gelatinase regulation. However the exact mechanism(s) remains to be investigated. Finally, evaluation of integrin αVβ3 associated mmp-2 expression and activity may add valuable information and can possibly be therapeutic target. The clinical exploitation of integrins will provide oncologists with novel therapeutic strategies for the treatment of malignancy in breast cancer.

关键词： Breast Cancer mmp-2 Alpha V Beta3 mt1-mmp TIMP-2 EMPRIN VEGF

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膜型基质金属蛋白酶-1的结构、功能与调节

生命的化学 2005年第6期25卷 468-471页

作者：蒋菊香阮长耿吴士良江苏省血液研究所血栓与止血室苏州215004 苏州大学医学院生物化学与分子生物学教研室苏州215123

膜型基质金属蛋白酶(membrane-type matrix metalloproteinase,mt-mmp)是一类基质金属蛋白酶家族的新成员,mt1-mmp是第一个鉴别出的膜型基质金属蛋白酶,它直接或间接降解细胞外基质中的多种成分,并对黏附分子有调节作用,被认为是mmp家... 详细信息

膜型基质金属蛋白酶(membrane-type matrix metalloproteinase,mt-mmp)是一类基质金属蛋白酶家族的新成员,mt1-mmp是第一个鉴别出的膜型基质金属蛋白酶,它直接或间接降解细胞外基质中的多种成分,并对黏附分子有调节作用,被认为是mmp家族中与肿瘤侵袭关系最密切的酶,具有独特的结构、功能与调节机制。

关键词： mt1-mmp 肿瘤侵袭调节机制

Egr-1 Mediates Si0_2-driven Transcription of Membrane Type Ⅰ Matrix Metalloproteinase in Macrophages

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2007年第1期27卷 13-16页

作者：向菲白明金阳马万里辛建保 Department of Respiratory Medicine Union Hospital Tongji Medical College Huazhong University of Science and Technology

The up-regulation mechanism of membrane type Ⅰ matrix metalloproteinase （mtI-mmp） in macrophages stimulated by silica in vitro and the contribution of early growth response 1 （Egr-1） transcription factor in the gene expression pathway were investigated. Macrophages stimulated by silica were treated with Egr-1 antibody or Egr-1 decoy oligodeoxynucleotides （ODN）. The levels of mt1-mmp proteins were determined by Western blot and the expression of mt1-mmp mRNAs was detected by RT-PCR. The results showed as compared with control macrophages, silica-stimulated group showed up-regulated gene expression of mt1-mmp via Egr-1 （P〈0.01）. Compared with silica-stimulated macrophages untreated with antibody, the cells treated with 5 μg/mL Egr-1 antibody were associated with reduced expression of mtI-mmp protein （P〈0.01） and mRNA （P〈0.01）. Compared with silica-stimulated untransfected group, the Egr-1 ＂decoy＂ ODN group was associated with reduction in the expression of mt1-mmp protein and mRNA （P〈0.01）. It was concluded gene expression of mt1-mmp which may play a critical role in silicosis was up-regulated by silica in macrophages. Egr-1 participated in the expression of mt1-mmp and positively regulated the expression. Both Egr-1 antibody and Egr-1 decoy ODN suppressed the expression of mtI-mmp through the Egr-1 pathway and may become a potential therapeutic tool in the management of silicosis in the future.

关键词： silicosis Egr-1 mt1-mmp decoy stratey macrophage

Expression of CD133 and Extracellular Matrix Molecules in Malignant Brain Tumors

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Neuroscience & Medicine 2011年第4期2卷 392-396页

作者： Seiichi Yoshida Toshiro Koike 不详

Background: CD133 could be characterized as a “stem-like” cell subpopulation and an invasive tumor phenotype. The objectives of this study were to investigate the relationship of CD133 and other remodeling factors such as matrix metalloproteinases (mmp) in the brain tumors. Methods: Tumors from 13 patients with brain tumors (8 lung cancer metastasis, 3 breast cancer metastasis, 2 gliomas) were studied to investigate the expression-patterns of CD133, EGFR, mt1-mmp, and mmp7 using the immunostaining and RT-PCR analysis. Results: EGFR immunostaining was detected in 75% (6/8) and 67% (1/3) of brain metastasis from lung adenocarcinoma and breast cancer, respectively. mt1-mmp immunostaining was also detected in 73% (8/11) of these brain metastasis. CD133 was not detected in these 13 patients. EGFR immunostaining was detected in 75% (6/8) and 67% (1/3) of brain metastasis from lung adenocarcinoma and breast cancer, respectively. mt1-mmp immunostaining was also detected in 73% (8/11) of these brain metastasis. CD133 was not detected in these 13 patients. Conclusions: The expression of CD133 indicates a marker for brain tumor initiating.

关键词： CD133 EGFR mt1-mmp mmp7 Brain Tumors

膜型基质金属蛋白酶-1在不同内皮细胞株中的表达差异

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中国生物化学与分子生物学报 2007年第11期23卷 916-920页

作者：蒋菊香马珍妮胡晓慧董宁征吴士良阮长耿苏州大学附属第一医院江苏省血液研究所苏州215006 苏州大学医学院生物化学与分子生物学教研室苏州大学医学院生化工程研究所苏州215123

为研究膜型基质金属蛋白酶-1(membrane-type matrix metalloproteinase-1,mt1-mmp)在血管生物学中的作用机制,比较了3株常用的内皮细胞株:人微血管内皮细胞株HMEC-1、人脐静脉内皮细胞株ECV304和EAhy926中mt1-mmp及与其功能相关的mmp-2,TIMP-2的表达差异.实时PCR和流式细胞术检测HMEC-1、EAhy926和ECV304中mt1-mmp/mmp-2/TIMP-2的表达,明胶酶谱法分析各细胞株上清中mmp-2的酶活.实时PCR结果显示,3株细胞均表达mt1-mmp与TIMP-2,mt1-mmp在EAhy926中表达最高,TIMP-2在ECV304中表达最高,而仅在EAhy926中检测到mmp-2的表达.流式细胞术和酶谱的结果与PCR结果基本一致.mt1-mmp和mmp-2在典型的大血管内皮细胞株EAhy926中高表达可能与该细胞独特的来源、表型特点和功能有关.

关键词： mt1-mmp 内皮细胞株表达差异