Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To measure matrix metalloproteinase (MMP) activity in a large number of samples it is advisable to use easily automated methods. We have evaluated and compared the activity of stromelysin-1 (MMP-3), matrilysin (MMP-7), 72 kDa gelatinase A (MMP-2) and 92 kDa gelatinase B (MMP-9) by zymogram analysis and fluorescent substrate degradation assays. FITC-casein and the fluorogenic peptide Dnp-Pro-beta-cyclo-hexyl-Ala-Gly-Cys(Me)-His-Ala-Lys-(N-Me-Abz)-NH 2 were used as fluorescent substrates. FITC-casein was more efficiently degraded than the fluorogenic peptide by all MMPs tested except MMP-9. MMP-2 was not significantly able to degrade the fluorogenic peptide. Gelatin zymography was the most sensitive method to detect the activity of both gelatinases but quantitation problems compromise its use. The degradation of fluorogenic substrates by MMPs could be inhibited by the chelating agent EDTA and by the tissue inhibitor of metalloproteinases 2 (TIMP-2), an MMP-specific inhibitor. Fluorometric methods represent a good alternative for MMP activity measurement, especially when a large number of samples must be processed.
Clin Exp Metastasis 1997 Jan
PMID:Evaluation of fluorometric and zymographic methods as activity assays for stromelysins and gelatinases. 900 3

We examined the production and tissue localization of matrix metalloproteinase-7 (MMP-7 = matrilysin) in human gastric carcinomas and analyzed the data in connection with the clinicopathological factors. Sandwich-enzyme immunoassay for the zymogen of MMP-7 (proMMP-7) showed enhanced production of MMP-7 in carcinoma tissues compared with control normal gastric mucosa. Immunohistochemical studies demonstrated that MMP-7 is localized predominantly to the carcinoma cells in 71% of the carcinoma samples (30/42 cases). The percentage of immunoreactive carcinoma cells to total carcinoma cells (positive ratio) was significantly higher in intestinal-type carcinomas (26%, median) than in diffuse-type carcinomas (3%, median) (p < 0.05). The positive ratio was markedly higher in carcinoma groups with vascular invasion (28%) or lymphatic permeation (12%) than in those without invasion (6%) or permeation (0%) (p < 0.05). It was also significantly higher in carcinoma groups with liver (49%) or lymph-node metastases (15%) than in those without metastases (6 and 2% respectively) (p < 0.05). Both proMMP-7 of 28 kDa and active MMP-7 of 19 kDa were detected in the carcinoma tissues by immunoblotting. Reverse-transcription-PCR showed specific amplification in 50% of the carcinoma cases (6/12 cases) and 8% of the normal control specimens (1/12 cases). In situ hybridization demonstrated that the carcinoma cells almost selectively express MMP-7 mRNA. These data suggest that enhanced production of proMMP-7 and its activation are implicated in invasion and metastasis of human gastric carcinomas.
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PMID:Expression and tissue localization of matrix metalloproteinase 7 (matrilysin) in human gastric carcinomas. Implications for vessel invasion and metastasis. 958 35

We examined production and tissue localization of 7 different matrix metalloproteinases (MMP-1, -2, -3, -7, -8, -9 and -13) and 2 tissue inhibitors of metalloproteinases (TIMP-1 and -2) in human endometrial-carcinoma tissues. Sandwich enzyme immunoassays showed enhanced production of MMP-7, MMP-8 and MMP-9 as well as TIMP-1 in the carcinoma tissues compared with non-carcinoma endometrial tissues. Among these MMPs, only the amount of MMP-7 correlated with clinicopathological factors of the carcinomas. The level was significantly 6.8-fold higher in the patient group with lymph-node metastases than in that without metastases (p < 0.05), and also increased with the progress of the clinical stage. MMP-7 was immunolocalized predominantly to the carcinoma cells in 73% of the cases, while MMP-8 and MMP-9 were immunostained in the inflammatory cells infiltrated in the carcinoma tissues. Immunoblotting revealed a definite band for the zymogen of MMP-7 (proMMP-7) of 28 kDa in 82% of the carcinoma samples, while only a faint band for proMMP-7 was seen in 57% of the non-carcinoma endometrial samples. Active MMP-7 species of 19 kDa and its activity were demonstrated in the carcinoma samples with proMMP-7 production by immunoblotting and zymography, respectively. RT-PCR using a specific primer pair for MMP-7 demonstrated expression in 86% of the carcinoma tissue and in 57% of the control tissue samples. In situ hybridization showed carcinoma cells selectively expressing MMP-7 mRNA. These data suggest that, among the 7 MMPs examined, MMP-7 may play a key role in invasion and lymph-node metastasis of human endometrial carcinomas.
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PMID:Enhanced production and activation of matrix metalloproteinase-7 (matrilysin) in human endometrial carcinomas. 1050 22

Uterine cervical adenocarcinoma typically is an aggressive neoplasm with a propensity for early invasion and dissemination; however, the regulatory mechanism of invasive activity of cervical adenocarcinoma cells has not been fully understood. In this study, biological effects of epidermal growth factor (EGF) and transforming growth factor (TGF)-alpha on invasion and proteinase expression of human cervical adenocarcinoma OMC-4 cells were investigated. Tumor cell migration along a gradient of substratum-bound fibronectin and invasion into the reconstituted basement membrane were stimulated by 0.1-10 nM EGF and TGF-alpha in a concentration-dependent manner. Their effects on tumor cell migration were also confirmed by wound assay. The zymography of tumor-conditioned medium showed that the treatment of OMC-4 cells with EGF and TGF-alpha resulted in the increase of matrix metalloproteinase (MMP)-2 and urokinase-type plasminogen activator (uPA). Matrilysin (MMP-7), also secreted by OMC-4 cells, was not affected by these growth factors. These results suggest that EGF and TGF-alpha act as positive regulators on the invasion of cervical adenocarcinoma cells, which may be associated with their stimulatory effects on tumor cell motility and the induction of type IV collagenase and uPA secreted by tumor cells.
Invasion Metastasis
PMID:Effects of EGF and TGF-alpha on invasion and proteinase expression of uterine cervical adenocarcinoma OMC-4 cells. 1064 Sep 3

The matrix metalloproteinases (MMPs) are important in tumour cell invasion and metastasis in many common cancers. However, relatively few studies have investigated the role of MMPs and their inhibitors, the tissue inhibitors of metalloproteinases (TIMPs), in leukaemia cell invasion. This study examined two leukaemia cell lines, K562 and HL-60 and showed that the K562 cell line was four times more invasive than the HL-60 cell line. The expression of MMP-2, matrilysin (MMP-7), MMP-9. TIMP-1, TIMP-2 and TIMP-3 was analysed. Both cell lines produced similar amounts of MMP-2, MMP-9 and TIMP-2. The K562 cells expressed more TIMP-1 than the HL-60 cells and neither cell line expressed TIMP-3. Interestingly, only the K562 cells expressed matrilysin suggesting a potential role for matrilysin in leukaemia cell invasion. in vitro invasion assays performed in the presence of a matrilysin blocking antibody showed a 40% reduction in invasive ability. This data suggests that matrilysin plays an important role in leukaemia cell invasion.
Clin Exp Metastasis 2000
PMID:The role of matrilysin (MMP-7) in leukaemia cell invasion. 1146 72

We studied the profile of four c-erbB receptors in head and neck squamous cell carcinomas (HNSCC) and to determine whether their expression was associated with clinicopathological features and key molecules involved in angiogenesis and metastasis. We also assessed the impact of expression on survival. This study included 54 cases of primary HNSCC, of which 27 cases showed lymph node metastasis. The expression of c-erbB receptors, matrix metalloproteinases (MMPs) and vascular endothelial growth factor (VEGF) family members was analysed in the same tissue homogenates by semi-quantitative RT-PCR. HNSCC frequently co-expressed multiple c-erbB receptors and showed significant correlations amongst their levels. High expression of epidermal growth factor receptor (EGFR), c-erbB-2 or c-erbB-3 was associated with an infiltrating mode of invasion, nodal metastases and advanced pathological stages. EGFR and c-erbB-2 levels were strongly correlated (P=0.0004-0.029) with the expression of MMP-2, MMP-7, MMP-9, MMP-10, MMP-11, MMP-13, VEGF-A and VEGF-C whereas the levels of c-erbB-3 and B-4 showed a weaker correlation (P=0.049-0.01) with some MMPs and VEGF-C. Only nodal metastasis and EGFR levels were significantly associated with poor outcome in uni- and multi-variate analysis. We conclude that co-operative signalling of all four c-erbB receptors may play a significant role in the pathogenesis of HNSCC. Amongst these, EGFR appears to be the dominant component controlling the invasive and angio-/lymphangiogenic phenotype in HNSCC via upregulation of multiple MMPs and VEGFs.
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PMID:C-erbB receptors in squamous cell carcinomas of the head and neck: clinical significance and correlation with matrix metalloproteinases and vascular endothelial growth factors. 1175 24

Invasion and dissemination of well-differentiated carcinomas are often associated with loss of epithelial differentiation and gain of mesenchymal-like capabilities of dedifferentiated tumor cells at the invasive front. However when analysing central areas of metastases of colorectal carcinomas one finds a regain of the differentiated epithelial growth patterns like in the primary tumor. More than 80% of these tumor have loss of function mutations in the APC tumor suppressor gene, leading to an overexpression of beta-catenine. In its nuclear pool beta-catenine acts as a transcription factor and is now considered as one of the main oncogenic proteins in colorectal carcinogenesis. We could define several molecules important for the processes of invasion and dissemination, like MMP-7, uPA, laminin-5, as target genes activated by nuclear beta-catenine. Moreover the characteristic phenotypic changes during tumor progression were associated with distinct expression patterns of beta-catenine and E-cadherin. Nuclear beta-catenine was found in dedifferentiated mesenchyme-like tumor cells at the invasive front, but strikingly, like in central areas of the primary tumors, was localized to the membrane and cytoplasm in polarized epithelial tumor cells in the metastases. This was accompanied by changes in the proliferative activity. Based on these data, we postulate that an important driving force for progression of well-differentiated colorectal carcinomas is the specific environment, initiating two transient phenotypic transition processes by modulating intracellular beta-catenine distribution in the tumor cells.
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PMID:[The Rudolf Virchow Prize 2001. The role of the oncoprotein beta-catenin ni the progression of colorectal cancers]. 1189 5

To clarify the mechanism of tumor metastasis, lymph nodes micrometastasis and expression of MMP-7, which is related to lymph node metastases, were investigated in 45 submucosal, invasive gastric carcinomas. Metastases to lymph nodes were detected in 12 of 45 cases(26.7%) by HE stain. In 13 of 45 cases (28.9%), only micrometastases were detected by immunostaining with anti-cytokeratin antibody. The incidence of micrometastases was higher in poorly-differentiated carcinoma than well-differentiated carcinoma. Expression of MMP-7 was higher in metastasis positive cases than in negative cases. In poorly-differentiated cases, expression of MMP-7 was associated with micrometastasis. In conclusion, expression of MMP-7 may play an important role not only in tumor metastasis but in micrometastasis to lymph node especially in poorly-differentiated cases.
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PMID:[Correlation between expression of MMP-7 in gastric submucosal invasive carcinoma and lymph node micrometastasis]. 1192 59

The ability of tumors to infiltrate the surrounding tissue is one of the major characteristics of a malignancy. This process is based on the tumors ability to destroy the extracellular matrix (ECM) including the basement membrane (BM). Several previous studies identified matrix metalloproteinases (MMPs), a family of zinc-dependent endopeptidases to be key players in this process. Since then multiple investigations focused on the expression and activation levels of their extracellular regulators and to a lesser extent of their transcriptional modulators. However, the exact diagnostic and prognostic values of these regulators still remain unclear. Squamous cell carcinomas of the head and neck (HNSCC) are known for their infiltrative growth and there is strong evidence that at least some members of the MMP-family play a crucial role in this process. It turned out that MMP-2, -9, -13 and to a lesser extent MMP-7 are related to the metastatic potential of HNSCC but further studies will be required to establish the exact role of MMPs in HNSCC. This Review will discuss the current literature concerning the role of MMPs in HNSCC.
Clin Exp Metastasis 2002
PMID:The role of matrix metalloproteinases in squamous cell carcinomas of the head and neck. 1209 Apr 67

Previous experimental and biochemical studies on matrix metalloproteinases (MMPs) have indicated that MMPs are implicated in cancer invasion and metastases. Studies on the expression of MMPs and tissue inhibitors of metalloproteinases (TIMPs) in various human cancer tissues have further demonstrated that activation of proMMP-2 mediated by a combination of TIMP-2 and MT1-MMP (the proMMP-2/TIMP-2/MT1-MMP system) correlates well with the progression of most of these cancers such as the breast carcinomas, thyroid papillary carcinomas, gastric adenocarcinomas, oral squamous cell carcinomas and gliomas, whereas MMP-7 plays an important role in the metastases of endometrial and gastrointestinal carcinomas. Although MMP-7 is a typical secreted MMP, a member of transmembrane 4 superfamily (TM4SF) captures proMMP-7 on the carcinoma cell membranes through interaction with its propeptide, leading to its pericellular activation. Thus, these results strongly suggest that proteolysis at the cell-extracellular matrix interfaces of cancer cells by the proMMP-2/TIMP-2/MT1-MMP and proMMP-7/TM4SF systems plays crucial roles in the progression of human cancers. In this article, we address the current views on the roles of these MMPs acting onthe cell membranes in human cancer invasion and metastases.
Cancer Metastasis Rev
PMID:MT1-MMP and MMP-7 in invasion and metastasis of human cancers. 1278 93


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