The role and significance of matrix metalloproteinase-7 in hepatobiliary diseases / 国际儿科学杂志

Matrix metalloproteinases(MMPs)are a large family of zinc-dependent endopeptidases, which are mainly synthesized by connective tissues, it can degrade the extracellular matrix(ECM)and basement membrane, affect the regeneration and reconstruction of normal tissues, and participate in the pathological process of malignant tumors.Matrix metalloproteinase-7(MMP-7)is the smallest member of the metalloproteinase family.It is expressed in many tissues of the body, such as thyroid, breast, lung, digestive tract, reproductive system and hepatobiliary system.In recent years, the expression of MMP-7 in hepatobiliary diseases has attracted more and more attention.MMP-7 is not only involved in the growth, metastasis and invasion process of hepatobiliary malignant tumors, but also highly expressed in liver fibrosis, biliary atresia and other diseases.This paper reviews the expression of MMP-7 in the above diseases.

ABCA8 promotes migration and invasion of human pancreatic cancer cells by activating ERK signaling pathway / 肿瘤

Objective: To investigate the effects of ABC-binding cassette transporter A subfamily 8 (ABCA8) on the migration and invasion of pancreatic cancer cells and the possible mechanism. Methods: Human pancreatic cancer CFPAC-1 cells were infected with the lentivirus GV358 carrying ABCA 8 gene or the empty vector lentivirus to establish ABCA8 overexpression cells or the control cells, respectively. The ABCA8 overexpression was confirmed by real-time fluorescent quantitative PCR and Western blotting. The effects of ABCA8 overexpression on the migration and invasion of CFPAC-1 cells were analyzed by wound healing assay and Transwell assay, respectively. The expression levels of extracellular signal-regulated kinase (ERK) and phospho-ERK (p-ERK) in ABCA8-overexpressed CFPAC-1 cells were detected by Western blotting. The effects of inhibiting ERK signaling by SCH772984 on ABCA8-mediated migration and invasion of CFPAC-1 cells were detected by Transwell assay. The expression levels of matrix metalloproteinases 2 (MMP2), MMP7, MMP9 and tissue inhibitor of metalloproteinase 1 (TIMP1) mRNAs in ABCA8-overexpressed CFPAC-1 cells were detected by real-time fluorescent quantitative PCR, and the expression levels of MMP7 and TIMP1 mRNAs in ABCA8-overexpressed CFPAC-1 cells treated with SCH772984 were detected by real-time fluorescent quantitative PCR. Results: ABCA8-overexpressed CFPAC-1 cells were successfully established. ABCA8 overexpression significantly promoted the migration (P 0.01) and invasion (P 0.05) of CFPAC-1 cells. The expression level of p-ERK protein was significantly elevated in ABCA8-overexpressed CFPAC-1 cells (P 0.01), and ERK inhibitor SCH772984 could eliminate the changes of ABCA8-induced migration and invasion of CFPAC-1 cells (both P 0.05). Meanwhile, ABCA8 overexpression could significantly upregulate MMP7 expression level (P 0.001) and downregulate TIMP1 expression level (P 0.01) in CFPAC-1 cells, and ERK inhibitor SCH772984 could eliminate the changes of MMP7 and TIMP1 expression levels induced by ABCA8 overexpression (both P 0.05). Conclusion: ABCA8-induced ERK signaling activation can enhance the migratory and invasive properties of human pancreatic cancer cells, which may be related to the upregulation of MMP7 expression and the downregulation of TIMP1 expression.

Expressions and Significance of MMP-7 and SDC-1 in Inflammatory Bowel Disease / 胃肠病学

Background: Matrix metalloproteinase-7 (MMP-7), a member of the MMPs family, is expressed in injured mucosal epithelial cells of many organs. Syndecan-1 (SDC-1), a substrate of MMP-7, plays an important role in tissue repair and maintaining intestinal barrier function. Aims: To investigate the expressions and significance of MMP-7 and SDC-1 in inflammatory bowel disease (IBD). Methods: Forty-five intestinal mucosa samples and fifty peripheral blood samples from inpatients with active IBD were collected during Jan. 2017 to Jan.2018 at the Second Affiliated Hospital of Zhengzhou University. Thirty intestinal mucosa samples and thirty-five peripheral blood samples from non-IBD subjects were served as controls. Expressions of MMP-7 and SDC-1 in intestinal mucosal tissue were detected by immunohistochemistry, and serum SDC-1 level was determined by ELISA. Results: MMP-7 was highly expressed in intestinal mucosal tissue of IBD patients, especially in mucosal epithelium bordering the ulcer area. Compared with control group, the expression of MMP-7 was significantly increased and that of SDC-1 was significantly reduced in intestinal mucosal tissue of IBD patients (P<0.05). In contrast, the serum level of SDC-1 was significantly increased in IBD patients (P<0.05). Spearman correlation coefficient analysis revealed a positive correlation between MMP-7 expression and the disease activity of IBD (rs=0.519, P<0.05 for ulcerative colitis; rs =0.583, P<0.05 for Crohn's disease), and a negative correlation between MMP-7 and SDC-1 in inflamed mucosa (rs=-0.646, P<0.05). Conclusions: Increased MMP-7 expression in intestinal mucosal tissue may contribute to the initiation and development of IBD via cleaving SDC-1 and impairing mucosal healing.

Association of mmp-7 -181A>G polymorphism with colorectal cancer and gastric cancer susceptibility: a systematic review and meta-analysis / Associação do polimorfismo mmp-7 -181a>G com câncer colorretal e suscetibilidade ao câncer gástrico: revisão sistemática e metanálise

ABSTRACT Introduction: The matrix metalloproteinase-7 (MMP-7) gene -181A>G polymorphism has been reported to be associated with colorectal cancer (CRC) and gastric cancer (GC) susceptibility, yet the results of these previous results have been inconsistent or controversial. Aim: To elaborate a meta-analysis to assess the association of -181A>G polymorphism of MMP-7 with CRC and GC risk. Methods: Published literature evaluating the association from PubMed, Web of Science, Google Scholar and other databases were retrieved up to April 25, 2018. Pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using random- or fixed-effects model. Results: A total of 19 case-control studies, which included eleven studies on CRC (2,169 CRC cases and 2,346 controls) and eight studies on GC (1,545 GC cases and 2,366 controls) were identified. There was a significant association between MMP-7 -181A>G polymorphism and GC risk under the homozygote model (GG vs. AA: OR=1.672, 95% CI 1.161-2.409, p=0.006) and the recessive model (GG vs. GA+AA: OR=1.672, 95% CI 1.319-2.554, p=0.001), but not with CRC. By subgroup analysis based on ethnicity, an increased risk of CRC and GC was found only among Asians. Conclusions: This meta-analysis suggests that MMP-7 -181A>G polymorphisms is associated with GC risk, but not with CRC. However, our results clearly showed that the MMP-7 -181A>G polymorphism significantly increased the risk of CRC only in Asians.

RESUMO Introdução: O polimorfismo da matriz metaloproteinase-7 (MMP-7) -181A>G tem sido relatado como associado à suscetibilidade dos cânceres colorretal (CRC) e gástrico (GC), mas os resultados desses estudos anteriores foram inconsistentes ou controversos. Objetivo: Elaborar metanálise para avaliar a associação do polimorfismo -181A> G da MMP-7 com o risco de CRC e GC. Métodos: Revisão da literatura publicada avaliando essa associação no PubMed, Web of Science, Google Acadêmico e outras bases de dados até 25 de abril de 2018. Odds ratio (OR) e o intervalo de confiança de 95% (IC) foram calculados usando dados aleatórios ou modelo de efeitos fixos. Resultados: Um total de 19 estudos caso-controle, que incluíram 11 trabalhos sobre CRC (2.169 casos de CCR e 2.346 controles) e oito sobre GC (1.545 casos de GC e 2.366 controles) foram identificados. Houve associação significativa entre o polimorfismo MMP-7 -181A>G e o risco de GC sob o modelo homozigoto (GG vs. AA: OR=1,672, IC 95% 1,161-2,409, p=0,006) e o modelo recessivo (GG vs. GA + AA: OR=1,672, IC 95% 1,319-2,554, p=0,001), mas não com CRC. Por análise de subgrupos com base na etnia, um risco aumentado de CRC e GC foi encontrado apenas entre os asiáticos. Conclusões: Esta metanálise sugere que os polimorfismos MMP-7 -181A>G estão associados ao risco de GC, mas não ao CRC. No entanto, estes resultados mostraram claramente que o polimorfismo MMP-7 -181A>G aumentou significativamente o risco de CRC apenas em asiáticos.

Significance of matrix metalloproteinase-7 and interferon inducible protein-10 in patients with rheumatoid arthritis-associated interstitial lung disease / 中华风湿病学杂志

Objective To evaluate early diagnostic value of matrix metalloproteinase 7 (MMP-7) and interferon inducible protein (IP-10) for rheumatoid arthritis-associated interstitial lung disease (RA-ILD).Methods Clinical and laboratory data and serum samples of patients with RA between March 2015 and June 2016 in our hospital were collected.Patients were subclassified as RA-without ILD,RA-with ILD,or RA-advanced ILD based on high-resolution computed tomography scans of the chest.Enzyme linked immunosorbent assay (ELISA) was used to assess MMP-7 and IP-10 in the serum of each group.The correlation between the two biomarkers and pulmonary function,the occurrence of ILD and other laboratory indexes were analyzed.Comparison of measurement data between the 3 groups was performed by single factor variance analysis,while count data was compared by Chi square test;the risk factors were analyzed by Logistic regression,receiver operating characteristic curve (ROC curve) was used to evaluate the diagnostic efficiency,correlation analysis was performed by Spearman correlation analysis.All statistical analysis was performed by Statistical Product and Service Solutions (SPSS) 19.0 statistical software.Results Serum levels of MMP-7 and IP-10 in RA-advanced ILD group and RA-mild ILD group were significantly higher than that of RA-without ILD group,the level of MMP-7 was [(1.9±3.0) ng/ml,(1.7±2.4) ng/ml,(0.2±0.2) ng/ml in turn,P＜0.05],IP-10 level was [(245± 394) pg/ml,(270±384) pg/ml,(38±26) pg/ml in turn,P＜0.05].And IP-10 level was significantly correlated with RA-ILD in both unadjusted and adjusted Logistic regression analyses,the values of OR were 1.024 and 1.023 respectively (P＜0.05).The ROC curves were plotted with MMP-7 and IP-10 respectively.The area under the curve (AUC) was 0.69 and 0.78 respectively.The AUC of combined detection increased to 0.83.Conclusion Levels of MMP-7 and IP-10 are elevated in the serum of RA patients with ILD,whether mild or advanced,supporting their value as pathogenically relevant biomarkers that may contribute to noninvasive detection of RA-ILD,and the combined estimate of them helps to improve the effectiveness of early diagnosis.

Significance and expression of zinc finger protein 139 and matrix metalloproteinase 7 in endometrial adenocarcinoma / 中国综合临床

Objective To observe the expression of ZNF139 and MMP-7 in endometrial adenocarcinoma tissues and discuss the correlation with clinical pathological significances.Methods In 71 patients diagnosed as endometrial adenocarcinoma,71 cancer tissues(adenocarcinoma group) and 71 adjacent normal tiuues(adjacent cancer group) were collected in operations.Immunohistochemical methods was used to detect the expression of ZNF139 and MMP-7 in the two groups,the relationship between the two genes and communication with clinicopathological indexes were discussed.Western blot and qRT-PCR were used to detected the expression of ZNF139 and MMP-7 at protein and mRNA level.Results The positive rates of ZNF139 was 66.20% in adenocarcinoma group,higher than in adjacent cancer group(21.42%,P=0.016);the positive rates of MMP-7 was 74.65% in adenocarcinoma group,higher than7 than in adjacent cancer group(26.76%,P=0.012).The expression of ZNF139 and MMP-7 was correlated with lymph node metastasis,muscle invasion and FIGO stage(P=0.028,0.031;P=0.004,0.016;P=0.008,0.011).Spearman rank correlation analysis showed there was positive correlation between ZNF139 and MMP-7 in adenocarcinoma tissues(r=0.716,P=0.039).Western blot showed that ZNF139 and MMP-7 expression in adenocarcinoma group were higher than in adjacent cancer group(t=6.92,7.34;P<0.01);qRT-PCR showed that ZNF139 mRNA and MMP-7 mRNA expression in adenocarcinoma group were higher than in adjacent cancer group(t=4.27,4.06;P<0.05).Conclusion ZNF139 and MMP-7 are correlated with malignant pathological characteristics in endometrial adenocarcinoma,they may modulate the malignant behavior together.

Clinical Value of Serum IL-17 and MMP-7 in Diagnosis of Hepatocellular Carcinoma / 中国医科大学学报

Objective To evaluate the significance of serum interleukin-17(IL-17)and matrix metalloproteinase-7(MMP-7)in the diagnosis of hepatocellular carcinoma(HCC). Methods A total of 52 patients with HCC(HCC group),32 patients with liver cirrhosis(LC group)and 36 healthy controls(control group)were enrolled for the study,and all samples were collected from The First Hospital of China Medical University. Serum levels of IL-17 and MMP-7 were determined using ELISA method. The diagnostic performance and their correlation was evaluated. Re-sults Serum levels of IL-17 and MMP-7 in HCC group were significantly higher than those in LC group(all P<0.001)and control group(all P<0.001). Both of them in LC group were higher than control group(all P<0.05). The area under ROC of serum IL-17 and MMP-7 were 0.901 (95%CI:0.847-0.954)and 0.845(95%CI:0.772-0.918). The sensitivity of serum IL-17 and MMP-7 in the diagnosis of HCC was 90.4%and 86.5%,respectively,and the specificity of the same markers was 77.9%and 76.5%,respectively. Combined detection of the two markers improved sensitivity to 98.7%and specificity to 94.8%. Serum IL-17 was positively correlated to MMP-7(r=0.513,P<0.01). Conclusion IL-17 and MMP-7 are involved in the progress of HCC,and serum IL-17 and MMP-7 may be useful markers in the diagnosis of HCC.

The expressions of CD151 and MMP-7 in lung adenocarcinoma tissues and their clinical significance / 肿瘤

Objective: To observe the expressions of CD151 and matrix metalloproteinase-7 (MMP-7) in lung adenocarcinoma tissues and their clinical significance. Methods: The expressions of CD151 and MMP-7 in 149 lung adenocarcinoma tissue samples and 40 adjacent normal tissue samples were detected by immunohistochemistry. The relationship between the expressions of CD151 and MMP-7 and their correlation with the clinicopathological data were analyzed. The disease-free survival (DFS)-related factors were examined. Results: The positive expression rates of CD151 and MMP-7 in lung adenocarcinoma tissues were higher than those in adjacent normal tissues (both P < 0.05). The CD151 expression was associated with smoking, lymph node metastases and TNM stage (all P < 0.05). The MMP-7 expression was associated with lymph node metastases and TNM stage (both P < 0.05). There was a positive correlation between CD151 and MMP-7 expressions in lung adenocarcinoma tissues (r = 0.322, P < 0.05). The DFS of patients with positive expression of CD151 was shorter than that of the patients with negative expression of CD151 (P = 0.005). The DFS of patients with coexpression of CD151 and MMP-7 was shorter than that of the patients with negative expressions of CD151 and MMP-7 (P = 0.004). CD151 was an independent DFS-related factor in patients with lung adenocarcinoma (P < 0.05). Conclusion: The positive expression rates of CD151 and MMP-7 are high in lung adenocarcinoma tissues. The DFS of patients with positive expression of CD151 is relatively short.

Expression of Matrix Metalloproteinase-7 and-19 in Liver Tissues of Rats with Biliary Atresia / 中国医科大学学报

Objective To detect the expression of matrix metalloproteinase (MMP)-7 and MMP-19 in the liver tissue of young rat models with biliary atresia (BA) and to explore their roles in progressive fibrosis.Methods Totally 132 Wistar newborn rats were subjected to common bile duct ligation (BDL) at day 3 after birth to establish animal models of biliary atresia.Sixty-two young rats served as the control group.Liver tissues were collected at days 3,7,14,21,and 28.Immunohistochemistry,Western blotting,and RT-PCR were used to detect the expression of MMP-7 and MMP-19.Results The BA models manifested cholestasis as early as 24 h after BDL.HE and Masson staining revealed progressive hepatic fibrosis.The expression of MMP-7 was observed to increase with time and was significantly higher in the experimental group when compared to control.The expression of MMP-19 was also found to gradually increase with time;however,it was lower than the control group.Conclusion MMP-7 and MMP-19 may be involved in the fibrosis of biliarv atresia.

Bio‑informatics analysis of renal carcinoma gene matrix metalloproteinase‑7.

BACKGROUND: Renal cancer is one of the common malignant tumors of the urinary system, seriously threatening human being’s health. The current discoveries, however, are far enough for efficient and secure treatment of renal cancer. AIMS: The aim was to explore the mechanism of matrix metalloproteinase‑7 (MMP‑7) protein in renal carcinoma cell metastasis by bioinformatics analysis. MATERIALS AND METHODS: Bioinformatics methods were used to analyze the composition of amino acids, as well as transmembrane structure, coiled coils, subcellular localization, signal peptide, functions and structures at all levels. RESULTS AND CONCLUSIONS: It showed that the gene MMP‑7 totally had 1131 bp. A peptide chain containing 267 amino acids was encoded in the coding region. Based on random coil, α helix, and further super‑helix, it had formed a stable neutral hydrophilic protein. The subcellular location analysis indicated that the protein was located outside the cell. The mature peptide started from the 18th amino acid, and its front‑end was the sequence of the signal peptide, belonging to the secreted protein. Analysis of the functional domain showed that this protein had two functional domains, the PG binding domain, and the zinc finger binding domain. Moreover, the protein, which was cross‑linked with it, was also one related to cancer cell proliferation and metastasis. To sum up, MMP‑7 is a stable neutral hydrophilic secreted protein, and it may play a vital role in the invasion and metastasis of cancer cells.

Effects of Weipixiao (胃痞消) on Wnt pathway-associated proteins in gastric mucosal epithelial cells from rats with gastric precancerous lesions / 中国结合医学杂志

<p><b>OBJECTIVE</b>To study the effects of Weipixiao (胃痞消, WPX) on Wnt pathway-associated proteins in gastric mucosal epithelial cells from rats with gastric precancerous lesions (GPL).</p><p><b>METHODS</b>Sprague Dawley rats were randomly divided into control, model, vitacoenzyme (0.2 g·kg(-1)·day(-1)), WPX high-dose (H-WPX, 15 g·kg(-1)·day(-1)), WPX medium-dose (M-WPX, 7.5 g·kg(-1)·day(-1)) and WPX low-dose (L-WPX, 3.75 g·kg(-1)·day(-1)) groups. After successfully establishing the GPL model, the rats were consecutively administered WPX or vitacoenzyme by gastrogavage for 10 weeks. Differential expression of Leucine-rich repeat-containing G-proteincoupled receptor 5 (Lgr5), matrix metalloproteinase-7 (MMP-7), Wnt1, Wnt3a, and β-catenin in gastric mucosal epithelial cells in all groups were immunohistochemically detected, and the images were taken and analyzed semiquantitatively by image pro plus 6.0 software.</p><p><b>RESULTS</b>Gastric epithelium in the model group showed significantly higher expression levels of Lgr5, MMP-7, Wnt1, Wnt3a and β-catenin than those of the control group(P<0.01). Interestingly, we also observed Lgr5+ cells, which generally located at the base of the gastric glandular unit, migrated to the luminal side of gastric epithelium with GPL. The expression levels of Lgr5, MMP-7, Wnt1, and β-catenin were all down-regulated in the L-WPX group as compared with those of both model and vitacoenzyme groups (P<0.05). A similar, but nonsignificant down-regulation in expression level of Wnt3a was noted in all WPX groups (P>0.05).</p><p><b>CONCLUSION</b>Our findings suggested that the therapeutic mechanisms of WPX in treating GPL might be related with its inhibitory effects on the expressions of Lgr5, MMP-7, Wnt1, β-catenin and the aberrant activation of Wnt/β-catenin pathway.</p>

Matrix metalloproteinase 7 expression in ampullary carcinoma.

Background: Matrix metalloproteinase 7 (MMP7) has largely been studied in pancreatic cancer which is the most common component of periampullary cancer in the western population. In India, the ampullary carcinoma is seen as the most common periampullary cancer in resected pancreaticoduodenectomies. We aimed to study the expression of MMP7 and its correlation with clinicopathological features in ampullary cancer. Materials and Methods: Consecutive cases of all ampullary cancer in a 3-year period were reviewed for histological differentiation (intestinal and pancreatobiliary) by morphology and immunohistochemistry (CDX2, MUC2, cytokeratin 20 [CK20], MUC1, cytokeratin 7 [CK7], and cytokeratin 17 [CK17]). All cases were stained for MMP7 and expression was correlated with histological variables, differentiation, and overall survival. Results: There were a total of 91 ampullary carcinomas (36 intestinal, 44 pancreatobiliary and 6 other types). Ampullary carcinoma showed MMP7 expression in 63.7% cases. Two-third of intestinal type and half of the pancreatobiliary type cancers showed MMP7 expression. MMP7 expression was signifi cantly higher in low pathological T-stage of total ampullary carcinomas; however, it was seen more commonly in higher overall stage of the pancreatobiliary type compared to intestinal type of ampullary carcinoma. Overall survival in patients with MMP7 expression was lower compared to MMP7 negative patients. Conclusions: This is the fi rst study on MMP7 expression in ampullary cancer. MMP7 expression was seen in nearly 64 % of ampullary cancer and showed a signifi cant correlation with low pathological (T-) stage and high overall stage with a shorter survival. MMP7 can be explored as a target for MMP inhibitor therapy in the future.

Expressions of MMP-7 and bFGF and their correlations with tumor interstitial microvascular density ;and cancer metastasis in NSCLC / 国际肿瘤学杂志

Objective To investigate the expressions of matrix metallopro-teinase-7 (MMP-7),basic fibroblast growth factor (bFGF)in NSCLC,and to elucidate the correlations among MMP-7,bFGF and MVD, as well as their relationships with cancer metastasis in NSCLC.Methods The expressions of MMP-7,bFGF and MVD were detected by immunohistochemical SP method in 80 cases of NSCLC and 40 cases of normal lung tissue,compare the expression of MMP-7 and bFGF in NSCLC and normal lung tissue,and then invest the rela-tionship between their expression and lymph node metastasis in NSCLC.The MVD was investigated within the CD34 positive slides,check the relationship between MVD and the expression of MMP-7 ,bFGF in NSCLC, and also its relationship with histology type,differentiation degree,lymph node metastasis and TNM stage. Results The positive ratesof MMP-7 and bFGF were significantly higher in NSCLC than those in normal lung tissue (70.0% vs 1 2.5%,χ2 =35.276,P =0.000;65.0% vs 1 0.0%,χ2 =32.41 1 ,P =0.000).The posi-tive rates of MMP-7 and bFGF were also significantly higher in group with lymph node metastasis compared to those group without lymph node metastasis (83.0% vs 51 .5%,χ2 =9.1 39,P =0.003;80.9% vs 42.4%,χ2 =1 2.584,P =0.000).The numbers of MVD were significantly higher in cases with MMP-7 and bFGF posi-tive expressions than those in cases with MMP-7 and bFGF negative expressions (46.78 ±1 1 .1 1 vs 31 .1 2 ± 7.62,t =5.831 ,P =0.000;45.05 ±1 0.97 vs 34.77 ±8.56,t =5.364,P =0.000).The number of MVD in group with lymph node metastasis was also significantly higher than that in group without lymph node metasta-sis (61 .32 ±21 .61 vs 40.52 ±1 8.31 ,t =3.865,P =0.008).The number of MVD in staging Ⅲ-Ⅳ group was significantly higher than that in stagingⅠ-Ⅱgroup (55.28 ±1 5.64 vs 41 .73 ±1 6.48,t =2.531 ,P =0.01 3).Conclusion The expression levels of MMP-7 and bFGF in NSCLC are high,and the positive rates of MMP-7 and bFGF are correlated with the lymphnode metastasis.The numbers of MVD are significantly higher in cases with MMP-7 and bFGF positive expressions than those in cases with MMP-7 and bFGF negative expre-ssions.MVD is correlated with lymph node metastasis and the TNM stage.It suggests that the expressions of MMP-7,bFGF and MVD may involve in the invasion and metastasis of NSCLC.

Analysis of serum matrix metalloproteinase-7 for diagnosis and prognosis in patients with bladder cancer / 中国医师杂志

ObjectiveThe aim of this study is to evaluate diagnostic and prognostic value of matrix metalloproteinase-7 (MMP-7) in patients with bladder cancer.MethodsA total of 77 patients with bladder cancer and 65 healthy controls were recruited in this study.The levels of serum MMP-7 were measured by ELISA methods.ResultsThe level of serum MMP-7 in bladder cancer group was significantly higher than those in the healthy control [ [ 3.1 (0 - 32.1 ) ng/ml vs 1.0 ( 0.2 - 2.6) ng/ml,x2 =9.29,P ＜0.01 ].The level of serum MMP-7 was correlated to lymph node metastasis ( x2=10.49,P ＜ 0.01 ) and tumor grade ( x2=4.55,P =0.033 ).Receiver operating characteristic ( ROC ) curves of serum MMP-7level was 0.810.Serum MMP-7 was used to diagnose bladder cancer with the sensitivity of 83.6％ and specificity of 77.4％.The survival rate in patients with a high level of MMP-7 was lower than that with a low level of MMP-7 (x2=3.88,P =0.0488).ConclusionsMMP-7 may be closely associated with the progression of bladder cancer.Serum MMP-7 may be a useful index for diagnosis and prognosis for patients with bladder cancer.

Triptolide inhibits ovarian cancer cell invasion by repression of matrix metalloproteinase 7 and 19 and upregulation of E-cadherin

Triptolide, a compound extracted from the traditional Chinese medicine preparation of Tripterygium wilfordii Hook F., has been reported to have anti-inflammatory and anti-cancer activities. However, its effect on ovarian cancer invasion is unknown. We observed that MMP7 and MMP19 expression increased in ovarian cancer tissue. Triptolide treatment inhibited the migration and invasion of ovarian cancer cells SKOV3 and A2780 at the concentration of 15 nM. We also observed that triptolide suppressed MMP7 and MMP19 promoter activity in a dose-dependent manner, down-regulating the expressions of these promoters on mRNA and protein level. Moreover, triptolide enhanced E-cadherin expression in ovarian cancer cells. In vivo, triptolide inhibited tumor formation and metastasis in nude mice, and suppressed MMP7 and MMP19 expression; it also enhanced E-cadherin expression in tumor in a dose-dependent manner. Over expression of MMP7 and MMP19, or suppression of E-cadherin expression partially abolished the inhibitory effect of triptolide on invasion of ovarian cancer cells. To summarize, triptolide significantly inhibited the migration and invasion of ovarian cancer cells by suppression of MMP7 and MMP19 and up-regulation of E-cadherin expression. This study shows that triptolide is a good candidate for the treatment of ovarian cancer and reduction of metastasis.

Influence of plasma matrix metalloproteinase-7 levels and genetic polymorphism of -181A/G on the stability of carotid plaque / 中华神经科杂志

Objective To explore the influence of plasma matrix metalloproteinase-7 ( MMP-7 ) levels and genetic polymorphism of MMP-7 - 181 A/G on the stability of carotid plaque.Method According to carotid ultrasound examination, 503 patients with carotid atherosclerotic lesions were consecutively recruited and divided into vulnerable plaque group (n = 118) and stable plaque group (n = 385).Plasma MMP-7 levels were measured by enzyme-linked immunosorbent assay (ELISA), and MMP-7 -181 A/G genotypes were determined by polymerase chain reaction-restiction fragment length polymorphism (PCR-RFLP).Results Plasma MMP-7 levels in carotid vulnerable plaque group were significantly enhanced as compared to stable plaque group (t =5.49, P =0.00).The frequency of MMP-7 -181G allele in vulnerable plaque group was significantly higher than that in stable plaque group (11.4% vs 7.0% ,χ2 = 4.78, P= 0.029).Compared to AA genotype, the genotypes with - 181G allele (AG + GG) significantly increased susceptibility to carotid vulnerable plaque ( χ2 = 5.01, OR = 1.81, P = 0.025 ) .When further analyzing the relationship between genotype and plasma MMP-7 levels, no significant differences of plasma MMP-7 levels were observed between AA genotype and AG + GG genotype in stable plaque group.However, in vulnerable plaque group, plasma MMP-7 levels of AG + GG genotype were significantly higher than that of AA genotype( t = 2.62, P = 0.01).Conclusion The present findings suggest that plasma MMP-7 level may be a biomarker for carotid vulnerable plaque.Genetic polymorphism of - 181 A/G in MMP-7 promoter may affect the expression of MMP-7, and seems to be implicated in susceptibility to carotid vulnerable plaque.

Expression and relationship between matrix metalloproteinase-7 and E-cadherin in gastric cancer / 肿瘤研究与临床

Objective To evaluate the expressions of MMP-7, E-cadherin in gastric carcinoma, and their relationship with tumor cell invasion and metastasis. Methods The MMP-7 mRNA and E-CD mRNA were detected by hybridization in situ in 78 gastric cancer tissues. Then analyze the relationship between the expression of MMP-7, E-CD and clinicopathological features. Results The expressions of MMP-7 and Ecadherin were significantly related with the invasion and metastasis of gastric cancer cell. The E-CD mRNA expression rate in MMP-7 mRNA positive gastric carcinoma tissue was much lower than that in negative carcinoma tissue (9.09 % vs 66.70 %). Conclusion Expression of MMP-7 mRNA and E-CD mRNA is associated with invasion, metastasis. Detection of MMP-7 mRNA and E-CD mRNA in bioptic specimens may be helpful in predicting tumor metastatic and recurrent potential and prognosis for patients with gastric carcinoma.

Significance of the expression of matrix metalloproteinases-7 in benign and malignant thyroid tissues / 中国医师杂志

Objective To investigate the expression of matrix metalloproteinases-7 (MMP-7) in benign and malignant thyroid tissues and its clinical significance. Methods The expression of MMP-7 in 50 thyroid cancers, 45 adenoma and 20 adjacent noncancerous portion tissues were studied by microwave-LSAB immunohistochemical method. Results The positive rate of MMP-7 in thyroid cancer was 64. 0%, which was significantly higher than 37. 0% in adenoma and 25.0% in adjacent noncancerous portion(X_2=8. 72,6. 52, P < 0.01 ). No correlation was observed between the expression of MMP-7 and histological grading of thyroid cancer. The expression of MMP-7 in lymph node metastasis and Grade Ⅲ～Ⅳ were both higher than that in negative cases and in Grade Ⅰ～Ⅱ ( P < 0. 05 ). The percentage of recurrence and death in MMP-7 positive cases were notably higher than that in negative cases( P <0. 05). Conclusion The expression of MMP-7 can be regarded as a parameter for evaluating the degree of malignancy, biological behavior and prognosis of thyroid cancer.

Expression and significance of E-cadherin and matrix metallopeptidase 7 in basal-like and Her-2 over-expressing breast carcinoma / 中华普通外科杂志

Objective To investigate the expression of E-cadherin and matrix metallopeptidase 7(MMP-7)and their significance in basal-like and Her-2 over-expressing breast carcinoma. Methods The protein expression of E-cadherin and MMP-7 were analyzed by immunohistochemical method in 20 cases of basal-like breast carcinoma and 21 cases of Her-2 over-expressing breast carcinoma.Statistical method was used to analyze the clinicopathological performance.Patients were followed up from 6 to 60 months.Results The ratio of basal-like breast carcinoma and invasive ductal carcinoma was 3.4%(20/501).the mean age was 49 years.The mean size of basal-like breast carcinoma(2.1 cm)was smaller than that of Her2 over-expressing breast carcinoma(3.0 cm)(P<0.05).The 5-year survival rate of patients with basal-like breast carcinoma was obviously(40.0%) lower than that of Her-2 over-expressing breast carcinoma (71.4%)(P<0.05),though,the 3-year survival rate was similar between the two groups.The protein expression of E-cadherin was down-regulated and even deficient in basal-like breast carcinoma(P<0.05).The protein expression of MMP-7 was higher in basal-1ike breast carcinoma than that in Her-2 overexpressing breast carcinoma(P<0.05).Conclusion Down-regulated expression of E-cadherin and upregulated expression of MMP-7 may be one of the mechanisms leading to high metastasis of basal-like breast carcinoma.

Metaloproteinases 1 e 7 e câncer colorretal / Metalloproteinases 1 and 7 and colorectal cancer

A metaloproteinase-1 (MMP-1) e a metaloproteinase-7 (MMP-7) são proteinases da matriz extracelular (MEC), zinco-dependentes, envolvidas no processo inicial da carcinogênese por permitirem a invasão tumoral na célula e promover o processo de metastatização. O polimorfismo dessas proteinases tem sido estudado recentemente com o objetivo de validar susa expressão e/ou atividade como marcador prognóstico. Evidências cumulativas revelam importante papel das MMP's 1 e 7 em diferentes fases da carcinogênese. A MMP-1 tem ação direta sobre a principal proteína da MEC, que é o colágeno do tecido intersticial conectivo. Sua expressão aumentada neste tecido pode indicar alto potencial de disseminação tumoral em diferentes tipos de câncer, incluindo o colorretal. A associação deste aumento da expressão também parece ser verdadeira para a MMP-7.

The metalloproteinase-1 (MMP-1) and metalloproteinase-7 (MMP-7) are proteinases of the extracellular matrix (MEC), zinc-dependent, involved in the initial process of carcinogenesis, allowing the invasion by the tumor cell and promoting the process of metastasis. The polymorphism of these proteinases has been studied recently in order to validate its expression and / or activity as a marker prognosis. Evidence shows cumulative important role of MMPs 1 and 7 in different stages of carcinogenesis. The MMP-1 is direct action on the main protein of the MEC, which is the collagen of interstitial connective tissue. Its increased expression in this tissue may indicate high potential for spread in different tumor types of cancer, including colorectal. The association of this increase of expression also appears to be true for MMP-7.