Expression of Matrix Metalloproteinase (MMP) and Tissue Inhibitors of Metalloproteinase (TIMP) mRNA in Conjunctival Melanoma Cell Lines
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Matrix metalloproteinase 9
Matrix Metalloproteinase 3
Matrix metalloproteinase inhibitor
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Background: Metalloproteinase 2 (MMP-2) and tissue inhibitor of metalloproteinase 2 (TIMP-2) participate in the degeneration of the extracellular matrix and are associated with carcinogenesis. MMP-2 is one of the main metalloproteinases active in neoplasia and is a marker of the malignant phenotype. Since the biological behavior of medullary thyroid carcinoma (MTC) varies widely, the present study was undertaken to determine if there is a correlation between the clinical evolution of MTC and the immunohistochemically detected expression of these enzymes in thyroid surgical specimens containing MTC. If so, their expression would be a novel indicator of the prognosis of MTC. Methods: Thirty-seven patients with MTC who had undergone thyroid surgery were followed for an average of 73 months. Immunohistochemical staining for metalloproteinase-related enzymes was performed in surgical paraffin blocks. The clinical status of the patients after surgery and at the end of the study period was characterized to determine correlations between these and the immunohistochemical markers. A value of p < 0.05 was considered statistically significant. Results: At the end of the study period, 15 patients (40.5%) were alive and without evidence of MTC, 17 (45.9%) had persistent MTC, and 5 (13.5%) had a relapse of their neoplasia. Four patients (10.8%) died during the course of the study. There was a significant correlation (p = 0.0005) between the immunohistochemical staining for MMP-2 and the clinical condition of the patients at the end of the study period, and a correlation between the state of apparent cure compared to persistence of MTC after thyroid surgery (p = 0.0207). No significant correlations were observed between either TIMP-2 expression or immune marking of metastatic lymph nodes and the clinical variables studied. Conclusion: Immunohistochemical expression of MMP-2 in thyroid surgical specimens from patients with MTC is a novel indicator of the prognosis of this cancer.
Matrix metalloproteinase 9
Medullary carcinoma
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Developmental and homeostatic remodeling of the extracellular matrix (ECM) is a highly regulated process orchestrated by a family of zinc-containing, calcium-dependent neutral proteases known as the matrix metallo-proteinases (MMP). This family of enzymes, which now contains twenty members, can collectively degrade all structural proteins of the ECM including interstitial collagens (I, II, III, and V), basement membrane collagens (IV), fibronectin, laminin, proteoglycan, and elastin (Table 1). The enzymatic activity of MMP family members is controlled by a group of inhibitor proteins known as the Tissue Inhibitors of Metalloproteinases (TIMPs), which consist of four family members (Table 2). Whereas all four TIMPs can inhibit all MMPs in vitro, preferential TIMP-MMP interactions and tissue-restricted TIMP expression suggest that each TIMP has a specific function (Table 2).
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目的:探讨基质金属蛋白酶-2(MMP-2)和组织基质金属蛋白抑制剂-2(TIMP-2)在人甲状腺乳头状癌组织中的表达及其与浸润程度、淋巴结转移的关系.方法:应用免疫组织化学S-P法对56例甲状腺乳头状癌组织及其癌旁正常甲状腺组织中MMP-2和TIMP-2表达情况进行检测.结果:MMP-2和TIMP-2在甲状腺乳头状癌组织中表达的阳性率分别为76.8%(43/56)和37.5%(21/56).在癌旁正常甲状腺组织中表达的阳性率分别为33.9%(19/56)和32.1%(18/56),表明MMP-2在甲状腺乳头状癌中有较高表达率.同时MMP-2和TIMP-2的表达与浸润程度、淋巴结转移有显著相关性(P＜0.05),与肿瘤大小无相关性.结论:MMP-2和TIMP-2的表达与甲状腺乳头状癌浸润程度、淋巴结转移密切相关,可作为判断甲状腺乳头状癌生物学行为和预后的参考指标.
Matrix metalloproteinase 9
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金属蛋白酶组织抑制剂(TIMP)家族是一类基质金属蛋白酶(MMP)的特异性抑制因子,TIMP-1是其成员之一.近年的研究发现,TIMP-1是一种多功能蛋白,除了抑制MMP的活性外,还对细胞的增殖有影响,并且对多种不同类型的细胞,如血细胞、乳腺细胞、肾小球系膜细胞、胰岛细胞等均有抗凋亡作用,且该作用多不依赖其抑制MMP的作用,而与多种酶和信号传导途径有关.该文对TIMP-1的生物学特点及在细胞增殖和凋亡中的作用作一综述。
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Matrix metalloproteinase 9
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Interstitial collagenase
Matrix metalloproteinase inhibitor
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Matrix metalloproteinase 9
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Matrix (chemical analysis)
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Scleritis is a severe and destructive inflammatory eye disease characterized by extensive extracellular matrix degradation. As in rheumatoid arthritis (RA), tissue destruction in scleritis may be mediated in part by matrix metalloproteinases such as collagenase (MMP-1) and stromelysin (MMP-3) which are normally kept in balance by endogenous inhibitors, such as tissue inhibitor of metalloproteinase (TIMP-1). To test this hypothesis, in situ hybridization was used to localize MMP-1, MMP-3 and TIMP-1 mRNA in diseased and normal scleral tissue using digoxigenin labelled probes. Strong expression of MMP-3 and TIMP-1 mRNA, but not MMP-1, was observed in the diseased scleral tissue. Infiltrating inflammatory cells such as macrophages and scleral fibroblasts were the primary source of MMP-3 and TIMP-1 expression. There was also relatively less TIMP-1 compared with MMP-3 mRNA expression in the inflammatory cells in scleritis tissue. In order to study regulation of metalloproteinase expression in ocular cells the authors established human scleral fibroblasts (HSF) in primary culture. Northern blot analysis was performed on total RNA extracted from HSF grown in serum free media. MMP-1 MMP-3 and TIMP-1 were constitutively expressed in these cells. Stimulation of HSF with pro-inflammatory cytokines likely to be present in scleritis, such as interleukin-1 (IL-1) and tumor necrosis factor (TNF), significantly induced MMP-3 and TIMP-1 mRNA expression. Using culture supernatants derived from the same cytokine stimulated scleral fibroblast the authors were able to detect MMP-3 protein production by Western blot analysis. They conclude that matrix metalloproteinase-3 mRNAs are present in scleritis tissue and may be induced by cytokines produced in the inflammatory process.
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