Polymorphisms of matrix metalloproteinase-7 and -9 are associated with oral tongue squamous cell carcinoma

Abstract Matrix degradation is an important event in the progression, invasion and metastasis of malignant head and neck lesions. Imbalances, mutations and polymorphisms of MMPs and their inhibitors are observed in several cancer subtypes. The aim of this study was to evaluate the association of the MMP-7 gene promoter (181 A/G) and MMP-9 (-1562 C/T) polymorphisms in oral tongue squamous cell carcinoma (OTSCC). MMP-7 (rs11568818) and MMP-9 (rs3918242) single-nucleotide polymorphisms (SNPs) were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis in 71 cases of OTSCC. Normal tissue specimens were obtained from 60 healthy volunteers to serve as the control. The MMP-7 G allele and MMP-9 T allele were more frequent in the OTSCC group than the control group, but only when these two SNPs were taken together was a significant association found with the nodal metastasis of OTSCC (p < 0.001). Based on our results, SNPs in the promoter region of MMP-7 and MMP-9 appear to be associated with greater risk of developing OTSCC, and with a higher propensity to form metastatic tumors. In this respect, molecular studies investigating polymorphisms may be useful in predicting tumor behavior.

Clinical value of biomarkers in diagnosis and treatment of idiopathic pulmonary fibrosis / 南方医科大学学报

Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial pneumonia characterized by progressive accumulation of fibroblastic foci and destruction of the alveolar structure. Due to an incomplete understanding of the mechanism of the occurrence and progression of IPF, currently no effective means have been available for its early screening or treatment. With a poor overall prognosis, the patients with IPF have a median survival of only 2-4 years. In recent years, several studies have confirmed that dozens of molecules are involved in the development of IPF and can be used as potential biomarkers. These biomarkers play important roles in early diagnosis (such as SP-D, MMP-7, and osteopontin), prognostic evaluation (such as telomerase length, KL-6, mtDNA, HSP-70, LOXL2, CXCL13, miRNA, ICAM-1, and CCL18), and guiding treatment of IPF (such as TOLLIP rs3750920 genotype, SAMS score, and SP-D), and also provide potential therapeutic targets (such as TERT, TERR, RTEC, and PARN).

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.

Post-surgical resection prognostic value of combined OPN, MMP7, and PSG9 plasma biomarkers in hepatocellular carcinoma / 医学前沿

Biomarkers for hepatocellular carcinoma (HCC) following curative resection are not currently sufficient for prognostic indication of overall survival (OS) and disease-free survival (DFS). The aim of this study was to investigate the prognostic performance of osteopontin (OPN), matrix metalloproteinase 7 (MMP7), and pregnancy specific glycoprotein 9 (PSG9) in patients with HCC. A total of 179 prospective patients with HCC provided plasma before hepatectomy. Plasma OPN, MMP7, and PSG9 levels were determined by enzyme-linked immunosorbent assay. Correlations between plasma levels, clinical parameters, and outcomes (OS and DFS) were overall analyzed. High OPN ( ⩾ 149.97 ng/mL), MMP7 ( ⩾ 2.28 ng/mL), and PSG9 ( ⩾ 45.59 ng/mL) were prognostic indicators of reduced OS (P < 0.001, P < 0.001, and P = 0.007, respectively). Plasma PSG9 protein level was an independent factor in predicting OS (P = 0.008) and DFS (P = 0.038). Plasma OPN + MMP7 + PSG9 elevation in combination was a prognostic factor for OS (P < 0.001). OPN was demonstrated to be a risk factorassociated OS in stage I patients with HCC and patients with low α-fetoprotein levels ( < 20 ng/mL). These findings suggested that OPN, MMP7, PSG9 and their combined panels may be useful for aiding in tumor recurrence and mortality risk prediction of patients with HCC, particularly in the early stage of HCC carcinogenesis.

mRNA and Protein Expression of AXIN,β-Catenin, MMP7 and MMP9 and Their Relationship in Lymphoma Cells / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the mRNA and protein expression of axin inhibitor (AXIN), β-chain protein (β-catenin), matrix metalloproteinase-7 (MMP-7) and matrix metalloproteinase-9 (MMP-9), and their relationship in lymphoma cells.</p><p><b>METHODS</b>The expressions of MMP-7, MMP-9, β-catenin and AXIN in lymphoma cell lines were detected by Western blot and RT-PCR. Moreover, the lymphoma cells with relatively low expression of AXIN were grouped and were transiently transfected by using pcDNA5-His-β-catenin and pCMV5-HA-AXIN; the protein and mRNA expression of MMP-7, MMP-9 and β-catenin in lymphoma cells was detected by Western blot and RT-PCR, respectively; the cell infiltration and migration ability in group with stable ligh expression of AXIN, group of interfering stable high expression of AXIN and blank control group were analyzed by transwell experiment.</p><p><b>RESULTS</b>The AXIN negatively correlated with MMP-7, MMP-9 and β-catenin expression in lymphoma cell lines. After the up-regulation of AXIN, the mRNA expression of MMP7, MMP-9 and β-catenin in Raji cells all not significantly changed, while the pratein expression of MMP-7, MMP-9 and β-catenin all significantly decreased (P<0.05); after the up-regulation of β-catenin, the mRNA and protein expression of MMP-7, MMP-9 was also up-regulated significantly (P<0.05). After interfering the AXIN, the mRNA expression of MMP-7, MMP-9 and β-catenin in group with stable high expression of AXIN all not changed significantly, while protein expression of MMP-7, MMP-9 and β-catenin was down-regulated significantly (P<0.05); after interfering the β-catenin, the protein and mRNA expression of MMP-7 and MMP-9 in group with stable high expression of AXIN all were down-regulated significantly(P<0.05).</p><p><b>CONCLUSION</b>The up-regulation of AXIN expression in lymphoma cells can lead to decrease of β-catenin expression and the resuts in significant decrease of MMP-7 and MMP-9 expression, there by plays a role to block the infiltration and migration of lymphoma cells.</p>

Metaloproteinasas de la matriz extracelular y su participación en el proceso de cicatrización / Matrix metalloproteinases and their participation in the healing process

RESUMEN Introducción: las metaloproteinasas son enzimas fundamentales para el mantenimiento estructural de la matriz extracelular, así como para su degradación en situaciones donde se requiere un proceso de reparación tisular. Objetivo: realizar una revisión de los aspectos más actuales de las metaloproteinasas y su papel en la cicatrización. Metodología de búsqueda: se realizó una revisión de 95 artículos, durante el período comprendido entre el 18 de julio de 2015 y 20 de septiembre de 2016 se utilizó las bases de datos Medline, Scopus, Scielo y Science Direct. Resultados: existen seis subfamilias de metaloproteinasas: colagenasas, estromalisinas, elastasas, gelatinasas, matrilisinas y las metaloproteinasas asociadas a la membrana plasmática. Las células endoteliales vasculares las secretan en donde hay daño epitelial y se requiere de un proceso de cicatrización. Conclusiones: las metaloproteinasas son endopeptidasas dependientes de zinc fundamentales para el mantenimiento y degradación de la matriz extracelular. Cuando el mecanismo de regulación falla y las metaloproteinasas tienen una sobreexpresión, ocurren procesos de cicatrización deficientes, condicionando la aparición de heridas crónicas, cicatrices hipertróficas o queloides, pterigión, fibrosis pulmonar y hepática, entre otras condiciones. MÉD.UIS. 2017;30(2):55-62.

ABSTRACT Introduction: Matrix metalloproteinases are essential for structural maintenance of extracellular matrix enzymes, as well as degradation in situations where tissue repair process is warranted. Objective: To review the most current aspects of matrix metalloproteinases and their role in the healing process. Research Methodology: A review of about 95 papers was conducted during the period from July 18, 2015 to September 20, 2016; PubMed, Scopus, Scielo and Science Direct were used. Results: There are six subfamilies of metalloproteinases: collagenases, stromalysins, elastases, gelatinases, matrilysins and metalloproteinases associated with the plasma membrane. Vascular endothelial cells secrete them where there is epithelial damage and a healing process is required. Conclusions: Metalloproteinases are zinc dependent endopeptidases that are essential for the maintenance and degradation of the extracellular matrix. When the adjustment mechanism fails and matrix metalloproteinases are overexpressed, poor healing processes occur, causing problems such as liver chronic wounds, keloids or hypertrophic scars, pterygium, pulmonary and liver fibrosis, among other clinical conditions. MÉD.UIS. 2017;30(2):55-62.

Overexpression of Axin inhibits lymphoma cell invasion and metastasis in vitro by down-regulating β-catenin and MMP7/MMP9 / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate that the role of Axin in regulating the invasion and migration ability of lymphoma cells and explore the molecular mechanisms.</p><p><b>METHODS</b>The expressions of Axin, β-catenin, MMP7, and MMP9 were detected in different lymphoma cell lines by RT-PCR and Western blotting. A lymphoma cell line with low Axin expressions was transiently transfected with pCMV5-HA-Axin and pcDNA5-His-β-catenin plasmid, and the expressions of β-catenin, MMP7, and MMP9 mRNA and protein were observed. A lymphoma cell model stably overexpressing Axin was transfected with AXIN-shRNA and β-catenin-shRNA, and the changes in β-catenin, MMP7, and MMP9 cexpressions were observed. The changes in the invasion and migration abilities of this cell model were assessed following Axin knockdown.</p><p><b>RESULTS</b>In the lymphoma cell lines tested, the Axin expression showed a negative correlation with β-catenin, MMP7, and MMP9 expressions. In Raji cells with a low Axin expression, overexpression of Axin resulted in decreased expressions of β-catenin, MMP7, and MMP9 at the protein levels but not the mRNA levels, and overexpression of β-catenin obviously increased MMP7 and MMP9 mRNA and protein expressions. In the cells with stable Axin overexpression, Axin knockdown caused increased expressions of β-catenin, MMP7, and MMP9 at the protein levels but not the mRNA levels, while β-catenin knockdown caused lowered expressions of MMP7 and MMP9 and suppressed cell invasion and migration.</p><p><b>CONCLUSION</b>In lymphoma cells, Axin overexpression can decrease the expression of β-catenin, which in turn decreases the expressions of MMP7 and MMP9 to inhibit the cell invasion and migration.</p>

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>

Association of matrix metalloproteinase -7 (-181A/G) promoter polymorphism in chronic pancreatitis.

Background & objectives: Chronic pancreatitis is progressive and irreversible destruction of the pancreas. Matrix metalloproteinase-7 (MMP-7) is a secreted matrilysin, which contributes to angiogenesis and breakdown of basement membranes of pancreatic tissues. The present study was aimed to investigate the association of MMP-7 −181A/G (rs11568818) gene promoter polymorphism in patients with chronic pancreatitis. Methods: A total of 100 chronic pancreatitis patients and 150 unrelated healthy individuals were included in this case control study. The genotyping of the MMP-7 gene (− 181 A/G) (rs11568818) was carried out based on PCR-RFLP. The serum levels of MMP-7 were determined by ELISA. Association between genotypes and chronic pancreatitis was examined by odds ratio (OR) with 95% confidence interval (CI). Results: The frequencies of the genotypes in promoter of MMP-7 were AA 49 per cent, AG 25 per cent and GG 26 per cent in chronic pancreatitis patients and AA 53 per cent, AG 38 per cent and GG 9 per cent in control subjects. Frequency of MMP-7 −181GG genotype and − 181G allele was significantly associated with chronic pancreatitis compared to healthy subjects [OR = 1.58 (95% CI: 1.06 –2.36), p =0.019]. There was no significant difference in the serum MMP-7 levels in the patients compared to control subjects. Interpretation &conclusions: The present study revealed a significant association of MMP-7 -181A/G (rs11568818) GG genotype with chronic pancreatitis patients, indicating its possible association with the disease.

Expressions of FOXC1 and MMP-7 in molecular subtypes of breast cancer and their association with clinicopathological characteristics / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the expressions of FOXC1 and matrix metalloproteinase 7 (MMP-7) in different molecular subtypes of breast cancer and their association with clinicopathological characteristics of the disease.</p><p><b>METHODS</b>Based on immunohistochemical results of ER, PR, HER2, CK5/6, CK14 and EGFR, 105 breast cancer patients were classified as 4 subtypes: luminal, HER2 positive, basal-like subtype (BLs) and normal breast-like subtype (NBLs). The association of FOXC1 and MMP-7 expressions with clinicopathological parameters in different molecular subtypes was analyzed.</p><p><b>RESULTS</b>Out of 105 patients with breast cancer, the subtypes of luminal, HER2 positive, BLs and NBLs accounted for 52.4% (55/105), 16.2% (17/105), 17.1%(18/105) and 14.3% (15/105), respectively. Patients with luminal and/or NBLs subtypes had significantly higher 5-year survival rate than those with HER2 positive and/or BLs did (log-rank=22.161, P<0.01). The overall positive expression rate of FOXC1 was 26.7% (28/105) and the expression was higher in BLs patients than that in other subgroups (χ²=30.108, P<0.01). The expression of FOXC1 was correlated with histological grade, tumor size, distant metastasis and 5-year survival rate of breast cancer. The overall positive expression rate of MMP-7 was 67.6% (71/105) and the expression of MMP-7 was also higher in BLs patients than that in other molecular subtypes (χ²=11.328, P<0.05). The positive expression of MMP-7 was correlated with metastasis in ipsilateral axillary lymph nodes, distant metastasis and 5-year survival rate of the patients. FOXC1 was correlated with MMP-7 (r=0.325, P<0.01).</p><p><b>CONCLUSION</b>Patients with luminal and/or NBLs breast cancer have more favorable prognosis than those with HER2 positive and/or BLs subtypes. The expressions of FOXC1 and MMP-7 are closely correlated with the clinicopathological features of breast cancer patients.</p>

The expression of tumor related macrophages and matrix solution element in laryngeal squamous carcinoma tissue and the relationship with tumor microvascular density / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To study the expression of CD68 antibody marked tumor associated macrophage TAMs and matrix solution element MMP-7 in laryngeal squamous carcinoma tissue and the relationship with clinicopathological parameters, so that to explore the relationship between the expression of the two molecular markers and laryngeal cancer tissue microvascular density (MVD).@*METHOD@#Immunohistochemical method was employed to detect the expression of CD68 and MMP-7 in 65 cases (laryngeal squamous carcinoma tissue in 45 cases; peritumoral nontumor tissue in 20 cases) and CD 34 antibody marked MVD expression.@*RESULT@#CD68 positive rate in squamous carcinoma tissue (82.2%, 37/45) is obviously higher than that in the peritumoral tissue (15%, 3/20) (P < 0.05), and MMP-7 positive rate in squamous carcinoma tissue is significantly different from that in peritumoral tissue (71.1%; 25%) (P < 0.05). The expression rate of CD34-MVD in laryngeal squamous carcinoma tissue( 26.52 +/- 6.36 )is higher than that in peritumoral tissue (12.23 +/- 4.01) (P < 0.05). In lymph node metastasis group, the positive expression rates of CD68 and MMP-7 are higher than those in the group without lymph node metastasis. MMP-7 showed no correlation with cancer stage, and CD68 was related with cancer stage; CD68, MMP-7 and CD34- MVD have positive correlation.@*CONCLUSION@#The high level of expression of TAMs and MMP-7 in laryngeal cancer tissue and the positive correlation with MVD illustrate that both of the markers play important roles in promoting laryngeal squamous carcinoma tissue metastasis and angiogenesis, which can be used as important markers to evaluate the invasion and metastasis of laryngeal cancer.

Immunohistochemical expression of matrix metalloproteinase-7 in human colorectal adenomas using specified automated cellular image analysis system: a clinicopathological study

To evaluate the immunohistochemical expression of matrix metalloproteinase-7 [MMP-7] in colorectal adenomas, and to correlate this expression with different clinicopathological parameters. The study was retrospectively designed. Thirty three paraffin blocks from patients with colorectal adenoma and 20 samples of non-tumerous colonic tissue taken as control group were included in the study. MMP-7 expression was assessed by immunohistochemistry method. The scoring of immunohistochemical staining was conducted utilizing a specified automated cellular image analysis system [Digimizer]. The frequency of positive immunohistochemical expression of MMP-7 was significantly higher in adenoma than control group [45.45% versus 10%] [P value < 0.001]. Strong MMP-7 staining was mainly seen in adenoma cases [30.30%] in comparison with control [0%] the difference is significant [P < 0.001]. The three digital parameters of MMP-7 immunohistochemical expression [Area [A], Number of objects [N], and intensity [I]] were significantly higher in adenoma than control. Mean [A and I] of MMP-7 showed a significant correlation with large sized adenoma [>/= 1cm] [P < 0.05], also a significant positive correlation of the three digital parameters [A, N, and I] of MMP-7 expression with villous configuration and severe dysplasia in colorectal adenoma had been identified [P < 0.05]. MMP-7 plays an important role in the growth and malignant conversion of colorectal adenomas as it is more likely to be expressed in advanced colorectal adenomatous polyps with large size, severe dysplasia and villous histology. The use of automated cellular image analysis system [Digmizer] to quantify immunohistochemical staining yields more consistent assay results, converts semi-quantitative assay to a truly quantitative assay, and improves assay objectivity and reproducibility

COX-2, MMP-7 expression in oral lichen planus and oral squamous cell carcinoma

OBJECTIVE@#To observe cyclooxygenase (COX)-2 expression in normal oral mucosa (NOM), oral lichen planus (OLP) and oral squamous cell carcinoma (OSCC) and explore its significance in the incidence of oral cancer.@*METHODS@#The immunohistochemical method and RT-PCR method were applied to detect the expression of COX-2 and MMP-7 in 10 cases with NOM, 33 cases of with OLP and 38 cases with OSCC.@*RESULTS@#The expression of COX-2 mRNA in OSCC tissues (68.4%, 26/38) was significantly higher than in the OLP (24.2%, 8/33) and NOM (0.0%, 0/10) (P<0.01). The expression of MMP-7 mRNA in OSCC tissues (65.8%, 25/38) was significantly higher than in the OLP (30.3%, 10/33) and NOM (0.0%, 0/10) (P<0.01). The expression of MMP-7 in OLP was significantly higher than in the NOM (P<0.05). There was no significant expression of COX-2 protein in NOM, and the positive rate was 42.4% (14/33) and 89.5% (34/38) in OLP and OSCC group, respectively. The COX-2 expression in cancer tissues was significantly higher than in NOM and OLP (P<0.05). The MMP-7 protein expression in cancer tissues (84.2%, 32/38) was significantly higher than in NOM (10.0%, 1/10) and in OLP (42.4%, 14/33), and the positive rate in OLP was significantly higher than in NOM (P< 0.01). The COX-2 expression was associated with clinical stage (P<0.05), the MMP-7 expression was associated with clinical stage and lymph node metastasis (P<0.05). The expressions of COX-2 and MMP-7 mRNA were positively correlated with OSCC.@*CONCLUSIONS@#The abnormal expressions of COX-2 and MMP-7 are closely related to the biological behavior of OSCC, the MMP-7 may be induced by COX-2, and further lead to the invasion and metastasis of OSCC.

Expression and significance of MMP-7, c-Jun and c-Fos in rats skin photoaging

OBJECTIVE@#To investigate the expression and significance of the MMP-7, c-Jun and c-Fos in rat photoaging skin.@*METHODS@#A total of 45 SD rats were randomly divided into control group, model group, natural recovery group, physiological saline injection group and dermal pluripotent stem cells transplantation (DMSCs group), model group, natural recovery group, physiological saline injection group. DMSCs were treated with UV lamp irradiation to establish light aging skin model. Rats were then sacrificed after model prepared, no treatment was processed in the natural recovery group. Saline injections was adopted in saline group, DESCs group was treated with DESCs transplantation. Rats were sacrificed after 4 weeks. The expression of MMP-7, c-Jun and c-Fos were detected using the immunohistochemical method.@*RESULTS@#In model group, MMP 7 positive expression was higher than that in the other 4 groups, but without statistically difference (P>0.05); c-Jun, c-Fos expression were higher than that in the control group and DESCs group (P0.05).@*CONCLUSIONS@#MMP-7, c-Jun and c-Fos can be used as diagnosis indicators in the early stage of light aging, and they jointly participate in its development. DMSCs transplants is effective in treating light aging skin.

Clinical Significance of Wnt/beta-Catenin Signalling and Androgen Receptor Expression in Prostate Cancer

PURPOSE: To investigate the relationships among the Wnt/beta-catenin pathway, androgen receptor (AR), and clinicopathological factors in hormone-naive prostate cancer. MATERIALS AND METHODS: This study was conducted with132 cases of hormone-naive prostate cancer treated by prostatectomy and prostate needle biopsy. An immunohistochemical study using antibodies against beta-catenin, matrix metalloproteinase-7 (MMP-7), and the AR was performed. For the in vitro study, PC-3, LNCaP, 22Rv1, and DU145 cell lines were used. RESULTS: The clinical or pathological stage ware a localized cancer in 36 patients (27.3%), locally advanced cancer in 31 (23.5%), and metastatic cancer in 65 (49.2%). We detected increased beta-catenin, AR, and MMP-7 expression with a high Gleason grade, disease progression, and increasing serum prostate-specific antigen (PSA) levels (p<0.01). In Spearman's rank correlations, the expression of cytoplasmic beta-catenin, MMP-7, and the AR were found to be significantly positively correlated. In addition, the expression of beta-catenin, MMP-7, and the AR were significantly correlated with clinicopathological variables indicative of a poor prognosis. Forty-nine patients with primary androgen deprivation had short response durations from hormone therapy to PSA progression with elevated MMP-7 expression on the Kaplan-Meier curve (p=0.0036). CONCLUSIONS: These data show that an activated Wnt/beta-catenin pathway and AR expression in prostate cancer are correlated with metastasis and aggressiveness. In addition, the expression of MMP-7 protein, a target of the Wnt/beta-catenin pathway, is associated with PSA progression in prostate cancer patients undergoing primary hormone therapy.

A new method of identifying the peripheral blood and the menstrual blood / 法医学杂志

OBJECTIVE@#To explore the tissue-specific gene expressions of the peripheral blood and the menstrual blood, and to search some specific factors to establish an effective method for identifying the peripheral blood and the menstrual blood.@*METHODS@#The specific products of the peripheral blood and the menstrual blood were detected by RT-PCR and separated by electrophoretic technology.@*RESULTS@#Beta-spectrin (SPTB) as one specific marker of peripheral blood and 18S rRNA as a kind of the housekeeping gene were expressed in both the peripheral blood and the menstrual blood. However, matrix metalloproteinase 7 (MMP7) as one specific marker of menstrual blood and human beta defensin 1 (HBD1) as one specific marker of vaginal discharge were only found in the menstrual blood.@*CONCLUSION@#There are differences of specific gene expressions between the peripheral blood and the menstrual blood. They could be accurately distinguished from each other by using the combination of fluorescence technology and RT-PCR to detect the specific identification of mRNA.

Effects of hydrostatic pressure in physiological range on bladder smooth muscle cells in vitro / 生物医学工程学杂志

To explore the effects of the physiological range of hydrostatic pressure on human bladder smooth muscle cells (HBSMCs) cultured in vitro, we used a hydrostatic compression device designed in our laboratory into the experiments, which were grouped by varied hydrostatic pressure gradients. Cellular morphology was observed with HE staining; cytoskeleton F-actin, cell cycle, both proliferating cell nuclear antigen (PCNA) and matrix metalloproteinase 7 (MMP-7) were detected respectively with immunofluorescence, flow cytometry and RT-PCR. We found that the proliferation, cytoskeleton and cycle distribution of HBSMCs were not obviously different among the groups of different hydrostatic pressure; however, the mRNA expression of MMP-7 exhibited a trend of first increasing and then declining as the pressure gradually rises. Thus the physiological range of hydrostatic pressure may not have significant influence on proliferation, morphology, skeleton, and cell cycle of HBSMCs, but it may have great effect on the expression of MMP-7.

Influence of Bushen Huoxue decoction on beta-catenin, MMP-7 of synoviocytes in rats with knee osteoarthritis / 中国骨伤

<p><b>OBJECTIVE</b>To observe beta-catenin expression of Wnt signaling pathway in rats with knee osteoarthritis, and influence of Bushen Huoxue decoction on beta-catenin and MMP-7 expression of synoviocytes in rats with knee osteoarthritis (OA).</p><p><b>METHODS</b>Rats model with knee osteoarthritis were established by Hulth method. Primary synoviocytes and OA synoviocytes were cultured with collagenase digestion method. The cultured synoviocytes were divided into normal group, OA model group and Bushen Huoxue decoction group. Western blotting method was used to detect beta-catenin, MMP-7 protein expression of synoviocytes after acting by Bushen Huoxue decoction for 48 h; ELISA method was used to detect MMP-7 expression of synovial supernatant.</p><p><b>RESULTS</b>OA synoviocytes were cultured successfully. Western blotting showed that beta-catenin, MMP-7 expression in OA synoviocytes was significantly higher than normal group, Bushen Huoxue decoction could significantly reduce beta-catenin, MMP-7 expression; ELISA results showed that MMP-7 expression of OA synovial supernatant was significantly higher than normal synoviocytes supernatant, Bushen Huoxue decoction significantly regulated the level MMP-7 down.</p><p><b>CONCLUSION</b>(1) High expression of beta-catenin in OA synoviocytes indicates that Wnt classical signal pathway is activated in rat with knee osteoarthritis; (2) High expression of MMP-7 expression in OA synoviocytes confirms the MMP-7 is downstream genes of Wnt/beta-catenin signal pathway; (3) Activation of Wnt signal pathway and increase of MMP-7 may cause degradation of articular cartilage, and promote the formation of osteoarthritis; (4) Bushen Huoxue decoction can reduce expression of MMP-7, and promote cartilage repair, which may be one of mechanisms of osteoarthritis.</p>

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.

Study on Association between Single Nucleotide Polymorphisms of MMP7, MMP8, MMP9 Genes and Development of Gastric Cancer and Lymph Node Metastasis / 대한소화기학회지

BACKGROUND/AIMS: Matrix metallopeptidase (MMP) is known to be involved in tumor invasion and metastasis of cancer. This study investigated the association of MMP7 rs11568818, MMP8 rs11225395, MMP9 rs17576 and rs2250889 with gastric cancer (GC) development and lymph node metastasis (LNM). METHODS: Samples were obtained from 326 chronic gastritis (CG) and 153 GC patients and genotyped by using the GoldenGate(R) method. Chi-square test was performed to identify the difference of allele distribution between each group (CG vs. GC; CG vs. with LNM GC). The associations of genotype with risk of GC and LNM were estimated by odds ratio and the 95% confidence interval was calculated by logistic regression adjusting for age and sex. RESULTS: The allele and genotype frequencies of MMP7 rs11568818, MMP8 rs11225395, MMP9 rs17576 and rs2250889 were not associated with the development of GC and LNM. CONCLUSIONS: In summary, MMP7 rs11568818, MMP8 rs11225395 MMP9 rs17576 and rs2250889 were not associated with the GC development and LNM in Korean population.