Home About us Contact | |||
Metalloproteinases MMP-2 (metalloproteinase + mmp-2)
Kinds of Metalloproteinases MMP-2 Selected AbstractsCorrelation of hypoxic signalling to histological grade and outcome in cartilage tumoursHISTOPATHOLOGY, Issue 5 2010Stephane Boeuf Boeuf S, Bovée J V M G, Lehner B, Hogendoorn P C W & Richter W (2010) Histopathology56, 641,651 Correlation of hypoxic signalling to histological grade and outcome in cartilage tumours Aims:, The molecular mechanisms underlying the progression of central chondrosarcoma are so far poorly understood. The aim of this study was to identify genes involved in the progression of these tumours by comparison of gene expression and correlation of expression profiles to histological grade and clinical outcome. Methods and results:, Array-based gene expression profiling of 19 chondrosarcoma samples was performed. Beside differences in the expression of cartilage matrix molecules, high-grade chondrosarcoma showed enhanced expression of the matrix metalloproteinase MMP-2 and of the hypoxia-inducible molecule galectin 1. Immunohistochemical analysis of galectin 1 and of further hypoxia-associated proteins was performed on 68 central and peripheral tumour samples. Hypoxia-inducible factor 1, (HIF-1,) activation was significantly elevated in high-grade central chondrosarcoma. A negative correlation of carbonic anhydrase IX expression to metastasis-free survival was independent of histological grade. Conclusions:, The expression patterns identified in this study point towards a substantial role for angiogenic and hypoxic signalling in chondrosarcoma progression. The constitutive activation of the transcription factor HIF-1, in high-grade chondrosarcoma could play a central role in the regulation of cell metabolism and vascularization in these tumours and may, for this reason, represent a potential target for chondrosarcoma therapy. [source] Expression of matrix metalloproteinases MMP-2, MMP-9 and their tissue inhibitors TIMP-1 and TIMP-2 in the epithelium and stroma of salivary gland pleomorphic adenomasHISTOPATHOLOGY, Issue 3 2009Xiaojun Zhang Aims:, The balance between matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) is involved in the morphogenesis of normal salivary gland as well as in the mechanisms of tumour invasion and metastasis. The role of MMPs and TIMPs in pleomorphic adenoma has not been elucidated sufficiently. Our aim was to analyse the mRNA and protein expression of MMP-2, MMP-9, TIMP-1 and TIMP-2 in the epithelium and stroma of pleomorphic adenoma and to evaluate their roles. Methods and results:, In each sample from six patients, cells from the epithelium and stroma were obtained by laser microdissection. The mRNA expression of MMPs and TIMPs was determined by real-time quantitative reverse transcriptase-polymerase chain reaction and protein expression was confirmed by immunohistochemistry. Results showed that mRNA expression of MMPs and TIMPs was significantly higher in stroma than in epithelium in most patients. MMPs and TIMPs were immunoreactive mainly in epithelium rather than in stroma. Conclusions:, Our results provide preliminary evidence that stromal myoepithelium may be the primary source of MMPs and that the stroma has the potential to play a more important role than ductal epithelium in biological behaviour of pleomorphic adenomas. These findings seem worthy of further investigation. [source] The prognostic value of p53, Ki-67 and matrix metalloproteinases MMP-2 and MMP-9 in transitional cell carcinoma of the renal pelvis and ureterINTERNATIONAL JOURNAL OF UROLOGY, Issue 11 2005SHUICHI KAMIJIMA Aim: To investigate the prognostic and predictive relevance of p53 protein, Ki-67 antigen, MMP-2 and MMP-9 in patients with transitional cell carcinoma (TCC) of the upper urinary tract. Methods: The expression of p53 protein, Ki-67 antigen, MMP-2 and MMP-9 was examined by immunohistochemistry in 69 patients with TCC of the upper urinary tract. Correlation of p53, Ki-67, MMP-2 and MMP-9 over-expression with conventional pathological parameters and patient survival was examined. Results: p53 over-expression was signi,cantly correlated with histological grade (P < 0.05), but not with pathological stage, vascular invasion, lymphatic invasion or lymph node metastasis. Ki-67 over-expression was signi,cantly correlated with stage, grade, lymphatic invasion and vascular invasion (P < 0.05). In survival analyses, Ki-67 over-expression was a signi,cant prognostic factor in the univariate analysis (P < 0.05), but it did not have a signi,cant impact on survival in the multivariate analysis. Ki-67 labeling index was a signi,cant prognostic factor in patients with a low p53 labeling index, but not in patients with a high p53 labeling index. Conclusion: Ki-67 over-expression is of prognostic value in TCC of the upper urinary tract, while p53, MMP-2 and MMP-9 are of limited value. [source] SYMPOSIUM: Clearance of A, from the Brain in Alzheimer's Disease: A,-Degrading Enzymes in Alzheimer's DiseaseBRAIN PATHOLOGY, Issue 2 2008James Scott Miners Abstract In Alzheimer's disease (AD) A, accumulates because of imbalance between the production of A, and its removal from the brain. There is increasing evidence that in most sporadic forms of AD, the accumulation of A, is partly, if not in some cases solely, because of defects in its removal,mediated through a combination of diffusion along perivascular extracellular matrix, transport across vessel walls into the blood stream and enzymatic degradation. Multiple enzymes within the central nervous system (CNS) are capable of degrading A,. Most are produced by neurons or glia, but some are expressed in the cerebral vasculature, where reduced A,-degrading activity may contribute to the development of cerebral amyloid angiopathy (CAA). Neprilysin and insulin-degrading enzyme (IDE), which have been most extensively studied, are expressed both neuronally and within the vasculature. The levels of both of these enzymes are reduced in AD although the correlation with enzyme activity is still not entirely clear. Other enzymes shown capable of degrading A,in vitro or in animal studies include plasmin; endothelin-converting enzymes ECE-1 and -2; matrix metalloproteinases MMP-2, -3 and -9; and angiotensin-converting enzyme (ACE). The levels of plasmin and plasminogen activators (uPA and tPA) and ECE-2 are reported to be reduced in AD. Reductions in neprilysin, IDE and plasmin in AD have been associated with possession of APOE,4. We found no change in the level or activity of MMP-2, -3 or -9 in AD. The level and activity of ACE are increased, the level being directly related to A, plaque load. Up-regulation of some A,-degrading enzymes may initially compensate for declining activity of others, but as age, genetic factors and diseases such as hypertension and diabetes diminish the effectiveness of other A,-clearance pathways, reductions in the activity of particular A,-degrading enzymes may become critical, leading to the development of AD and CAA. [source] Immunohistochemical expression of vascular endothelial growth factor, matrix metalloproteinase 2, and matrix metalloproteinase 9 in cutaneous melanocytic lesionsCANCER, Issue 9 2002M.D., Oriana Simonetti Ph.D. Abstract BACKGROUND Vascular endothelial growth factor (VEGF), an endothelial cell mitogen, plays a hierarchical role in regulating physiologic and pathologic angiogenesis. Moreover, the transformation from noninvasive to invasive carcinomas is accompanied by focal disruption and discontinuity of the basement membrane. Several groups of proteases have been implicated in tumor cell invasion, including the 72-kDa gelatinase A/Type IV collagenase (matrix metalloproteinase 2 [MMP-2]) and the 92-kDa gelatinase B/Type IV collagenase (MMP-9). METHODS The authors assessed the immunohistochemical expression of VEGF and metalloproteinases MMP-2 and MMP-9 in paraffin embedded biopsy specimens of malignant melanomas (18 invasive melanomas and 10 in situ melanomas); dysplastic nevi with architectural disorder and cytologic atypia of melanocytes; Spitz nevi; and compound or predominantly intradermal, ordinary, benign melanocytic nevi. RESULTS Strong cytoplasmic staining for VEGF was observed in melanoma cells in as many as 77% of primary invasive melanomas, whereas only 25% of the in situ melanomas exhibited a detectable immunoreactivity for VEGF. It is interesting to note that no immunoreactivity was shown by any nevi; Spitz nevi, in particular, showed negative immunoreactivity to VEGF. Invasive melanomas and in situ melanomas displayed coexpression of MMP-2 and MMP-9, although to a variable extent. In particular, high MMP-2 staining was observed in 14 of 18 invasive melanomas; moreover, strong MMP-2 expression also was observed in 60% of in situ melanomas, whereas the residual 40% of those melanomas showed a moderate level of positivity. CONCLUSIONS On the basis of the current data showing that malignant melanocytic tumors displayed strong VEGF expression, whereas benign melanocytic proliferations showed no immunoreactivity for VEGF, VEGF also may be used as a discriminating factor to distinguish malignant melanoma from lesions of uncertain histology. Cancer 2002;95:1963,70. © 2002 American Cancer Society. DOI 10.1002/cncr.10888 [source] |