Difference In Expression Of MMP-2 Research Articles

Differences in MMP-2 Expression in High- and Low-Grade MPNST and its Correlation with Prognostic Factors

Malignant peripheral nerve sheath tumor (MPNST) is a soft tissue sarcoma, which is difficult to distinguish from other spindle cell sarcomas. MPNST is hostile, with a high recurrence, and tends to metastasize hematogenously, especially to the lungs. A phase of the metastasis is a degradation of the extracellular matrix, where Matrix Metalloproteinase (MMP) plays an essential role in this process. Gelatinase-type MMP, MMP-2 and MMP-9, can degrade basal membrane and fibrillar collagen to open the invasion pathway. MMP-2 can degrade more collagen and non-collagen extracellular matrix than MMP-9. Therefore, the study aimed to see the relationship between MMP-2 overexpression and histopathological malignancy grading and other clinical prognostic variables. The study was conducted by immunohistochemical staining of MMP-2 in 39 cases, consisting of 19 cases of low-grade MPNST and 20 cases of high-grade MPNST. Subsequently, an analysis of the relationship between MMP-2 overexpression and the malignancy grading and clinical variables was performed, such as age, sex, and tumor size and location. MMP-2 overexpression was seen in 19 (95%) cases of high grade and three (15.8%) cases of low-grade MPNST (p 0.000). The study also found a significant relationship between MMP-2 overexpression and histopathology grading, which may be helpful to define the prognosis.

Immunohistochemical Profiles of Matrix Metalloproteinases and Vascular Endothelial Growth Factor Overexpression in the Antoni B Area of Vestibular Schwannomas

To evaluate the clinical manifestations of cystic vestibular schwannomas (VSs), investigate the immunohistochemical profiles of matrix metalloproteinases (MMPs) and vascular endothelial growth factor (VEGF) expression in Antoni A and B areas, and speculate the pathogenesis of cystic formation and intratumoral hemorrhage. Clinical features and outcomes of 24 cases of cystic VSs and 38 cases of solid VSs were retrospectively compared. Immunohistochemical studies were conducted to evaluate the characteristics of MMPs and VEGF in cystic and solid VSs. The tumor size was 38.92 ± 1.86 mm and 31.95 ± 1.74 mm in the cystic and solid VSs group, respectively (P= 0.011). Cystic VSs were rich in the Antoni B area. MMP-9 expression was low in the Antoni A and B areas. MMP-2 was moderately expressed. No significant difference in MMP-2 expression existed between the Antoni A and B areas (P > 0.05). VEGF and MMP-14 expression were moderate in the Antoni A area and intense in the Antoni B area, and the expression of both was significantly greater in the Antoni B area than in the Antoni A area (P < 0.001). MMP-14 and VEGF expression were significantly greater in the Antoni B area than in the Antoni A area. Upregulated MMP-14 may degrade loose collagen in the Antoni B area and contribute to cystic formation. MMP-14 can enhance VEGF activity, which may induce extravasation of a plasma ultrafiltrate, cystic expansion, and intratumoral hemorrhage. Therefore, MMP-14 inhibition may be a therapeutic strategy for treating cystic VSs.

Expression of matrix metalloproteinase -2 in Breast cancer

Formalin-fixed , paraffin embedded blocks tissue for thirty one breast cancer patients were obtained from the archive of the Pathology laboratory of Al-Yarmouk Teaching Hospital from January 2011 to July 2012 . In addition Formalin-fixed , paraffin embedded blocks tissue for ten fibroadenoma of breast were collected and used as control group . These blocks were subjected to cut as serial thin sections of (4μm) thickness and were sticked on positive charge slides to be used for in situ hybridization for the detection of matrix metalloproteinase -2 in breast cancer (MMP-2) . Overexpression of MMP-2 was detected in 90.3% (28 out of 31) of breast cancer samples (&gt; 50% of the cells appearing as positive) . The remaining 3 samples (9.7%) showed a weak- moderately expression (&lt; 50% of the cells appearing as positive) . The statistical analysis demonstrated a highly significant differences in MMP-2 expression among patients with breast cancer when compared with fibroadenoma of breast patients (control group) . In conclusion MMP-2 plays an important role in pathpgensis of breast cancer and supports the evidence of its role in evolution , progression and cell survival of breast cancer .

Gelatinases and their tissue inhibitors are associated with oxidative stress: a potential set of markers connected with male infertility.

The expression and activity of matrix metalloproteinases (MMPs) may be regulated by oxidative stress in various pathophysiological processes; therefore, the aim of the present study was to analyse the associations between the expression of the gelatinases MMP-9 and MMP-2 and their tissue inhibitors TIMP-1, TIMP-2 and levels of total antioxidant capacity (TAC) and advanced oxidation protein products (AOPP) in seminal plasma prepared for artificial insemination. Levels of MMPs and TIMPs were evaluated using ELISA, whereas TAC and AOPP in the seminal plasma of 131 childless men and 38 fertile volunteers were determined spectrophotometrically. Seminal MMP-9 expression was higher in childless men than in fertile subjects, whereas there was no significant differences in MMP-2 expression between the analysed seminal groups. TIMP-1 and TIMP-2 expression was similar in all groups. However, TAC expression was significantly higher in infertile normozoospermic and oligozoospermic men and AOPP expression was higher in astheno-, oligo- and normozoospermic infertile patients than in fertile men. High AOPP, together with an increased MMP-9:TIMP-1 ratio alters the oxidative-antioxidative balance of the ejaculate, thereby reducing male fertility, and therefore these parameters may serve as additional diagnostic markers of semen quality and male reproductive potential.

184 FOLLICULOGENESIS AND DONOR AGE INFLUENCE MATRIX METALLOPROTEINASE-2 EXPRESSION IN THE DOMESTIC CAT

Matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) are known to play key roles in the remodelling of extracellular matrix during ovarian folliculogenesis, especially during the final stage of follicle development. To date, little is known about the significance of MMPs and TIMPs during preantral follicle development. This study determined the expression of MMPs and TIMP-1 during various stages of cat folliculogenesis, largely for the purpose of securing information useful to improving in vitro follicle culture. Primordial (~10 follicles/cat), primary (~5 follicles/cat), secondary (~9 follicles/cat), early antral (~9 follicles/cat), and antral (~4 follicles/cat) follicles were physically isolated from ovaries recovered from 15 cats (5 months to 3 years old during follicular stage) undergoing ovariohysterectomy and assessed for expression of MMP-1, -2, -3, -7, -9, and -13 as well as TIMP-1 using real-time quantitative polymerase chain reaction (q-PCR; 2–4 replicates/follicle stage). Additional ovaries were obtained from three prepubertal (6 months old) and three adult (1 year old) cats and ovarian pieces were fixed in Bouin's solution and assessed for MMP-2 and -13 localization using immunohistochemistry. MMP expression data were analysed using the Kruskull-Wallis one-way ANOVA. Follicles from all stages of development expressed MMPs and TIMP-1. Specifically, expression of MMP-2 increased (P &lt; 0.05) as folliculogenesis progressed (10-fold increases from primordial to early-antral and antral stage). There were no differences (P &gt; 0.05) in the expression of other MMPs among follicular classes. For TIMP-1, there was a tendency (P = 0.07) for increased expression after antrum formation (early antral and antral stages). Immunohistochemistry analysis revealed that MMP-2 was expressed in both the oocyte and somatic cells of all follicular stages in prepubertal cats. However, MMP-2 expression was limited to granulosa and theca cells of antral follicles in adult females. MMP-13 was expressed in the granulosa and theca cells of primary, secondary, and antral stage follicles, and there were no differences (P &gt; 0.05) in localization patterns for this protein between prepubertal and adult females. In summary, the study is the first to report the expression of MMPs as well as TIMP-1 in isolated cat follicles. The difference in MMP-2 expression between prepubertal and adult cats suggests that there may be age-specific requirements for in vitro follicle growth. We are keenly interested in this information for underpinning the development of new in vitro microenvironments for growing immature cat follicles. We suspect that such information will be crucial for understanding how to promote the remodelling of the extracellular matrix by creating degradable biomaterials containing MMP-sensitive peptides to allow optimal follicle expansion.

Comparative immunohistochemical study of ameloblastoma and ameloblastic carcinoma

Ameloblastic carcinoma combines the histologic features of ameloblastoma with cytologic atypia, regardless of whether it has metastasized. Because of its rarity, there are few immunoprofile studies of ameloblastic carcinoma and few comparative studies of ameloblastic carcinoma and ameloblastoma. In this study, we compared the expression levels of cytokeratins (CKs), matrix metalloproteinases (MMPs), and Ki-67 between ameloblastoma and ameloblastic carcinoma, and assessed the usefulness of these markers for differentiating the tumors. We assessed CK7, CK14, CK18, CK19, MMP-2, MMP-9, and Ki-67 expression by immunohistochemistry in 10 cases of ameloblastoma and 7 cases of ameloblastic carcinoma and then compared expression patterns between the 2 groups. Immunostaining for CK14 and CK19 was diffuse and strongly positive in both tumor types, but staining for CK7 was focally positive in only 1 case of ameloblastoma and absent in all cases of ameloblastic carcinoma. However, there was a significant difference in CK18 expression between the 2 tumors (P = .000). Whereas 80% of ameloblastomas showed negative reactivity for CK18, most cases of ameloblastic carcinomas showed a moderate to strong intensity of immunostaining for CK18. Regarding the expression of MMPs, there were significant differences in parenchymal MMP-2 and stromal MMP-9 expression between the 2 tumors. Compared to ameloblastoma, ameloblastic carcinoma showed significantly strong expression of MMP-2 in parenchymal cells (P = .001) and MMP-9 in stromal cells (P = .013). However, there were no differences in MMP-2 expression of stromal cells and MMP-9 expression of parenchymal cells between ameloblastoma and ameloblastic carcinoma. The mean Ki-67 labeling index (LI) of ameloblastic carcinomas was 17.21%, which was significantly higher than that of ameloblastomas (3.57%; P = .002). The significant expression of CK18, parenchymal MMP-2, stromal MMP-9, and Ki-67 could provide useful markers for differentiating ameloblastic carcinoma from ameloblastoma.

Expression of matrix metalloproteinases and aggrecanase in the synovial fluids of patients with symptomatic temporomandibular disorders

To investigate whether matrix metalloproteinases (MMPs) and/or aggrecanase in synovial fluid can be used as biochemical markers in the diagnosis of internal derangement (ID) of the temporomandibular joint (TMJ). Forty-four samples of synovial fluid were obtained from 35 patients with ID and osteoarthritis (OA) and 15 normal samples from 10 asymptomatic volunteers. MMP-2, -9, and aggrecanase in the synovial fluid were examined by immunoblotting. The incidences of MMP-2, -9, and aggrecanase expression in the ID and OA group were significantly higher than those in the normal group (P < .05). Those with anterior disc displacement without reduction and severe OA showed significantly high expression of MMP-9 compared with other disease subgroups (P < .05). Conversely, comparatively high expression of MMP-2 and aggrecanase was shown in the early-stage OA group. However, there was no significant difference in expression of MMP-2 and aggrecanase among disease subgroups. These findings suggested that expression of aggrecanase could be a potential biochemical marker for articular cartilage degradation in ID of the TMJ.

Normobaric hyperoxia therapy exerts its neuroprotective effect through an increase in tissue pO2 and a decrease in free radical generation, caspases and MMP expression in the ischemic penumbra

Stroke is a leading cause of death and disability. However, current treatments are ineffective. Oxygen therapy aimed at increasing tissue pO2 has been used as a potential treatment modality. Unfortunately, most experiments with oxygen therapy were conducted without monitoring the actual interstitial pO2 level that is essential for penumbral tissue to survive, and also a critical parameter for evaluation of the efficiency of oxygen therapy. Using the unique capability of in vivo electron paramagnetic resonance (EPR) oximetry to measure localized interstitial pO2, we have conducted EPR-guided oxygen therapy by monitoring penumbral pO2 in a rat model of 90-min transient ischemia while normobaric hyperoxia is administered. Our results reveal that penumbral pO2 level can be modulated by changing the percentage of oxygen content in the breathing gas, and that 95% O2 given to rats is capable of raising penumbral interstitial pO2 close to the physiological (pre-ischemic) value during ischemia. However, 95% O2 also caused an increase in penumbra pO2 to a level that was twice as high as the pre-ischemic level when given during reperfusion. Oxygen therapy with 95% O2, begun immediately after ischemia and continued for 90-min significantly reduced infarction volume by 40% and improved neurological function. Oxygen therapy given upon reperfusion also reduced infarction volume by 15%, but it was not statistically significant. In order to investigate the possible molecular mechanism for the observed neuroprotective effect of hyperoxia treatment, we have studied the effects of oxygen therapy in the ischemic penumbra. We focused specifically on the generation of free radicals and the activation of matrix metalloproteinase (MMP) and caspase, two well characterized mechanisms leading to cerebral injury that are regulated through free radical generation. Our results demonstrate that 95% O2 treatment administered during the 90-min ischemia decreased the formation of 8-hydroxy-2'-deoxyguanine, a biomarker of oxidative DNA damage. Furthermore, 90-min ischemia dramatically increased the MMP-2 and 9 expression at 24 hrs post reperfusion, while hyperoxia treatment decreased penumbral MMP-9 expression by 50%. Interestingly, there was no difference in MMP-2 expression between the oxygen treated and non-treated groups. Similarly, 90-min cerebral ischemia induced approximately a 100% increase in 22 kD cleaved caspase-8 and a 25% increase in 43 kD cleaved caspase-8 in the penumbra, as compared to the contralateral side during normoxia. Hyperoxia treatment significantly decreased caspase activation in the penumbra. These results establish for the first time that normobaric hyperoxia oxygen therapy exerts its neuroprotective effect during ischemia through the increase of penumbral tissue pO2, which leads to a reduction in free radical generation, and consequently, caspases and MMPs expression.

The expression of matrix metalloproteinases and their tissue inhibitors in pleomorphic adenoma

To examine the expression of MMPs and TIMPs in pleomorphic adenoma of salivary gland and to investigate the relationship between the expression and the biological behaviour of the tumor. Twenty-three cases of pleomorphic adenoma were divided into active type and common type according to their biological behavior. Immunohistochemistry for MMP-2, MMP-9, TIMP-1, TIMP-2 and gelatin zymography analysis were performed in these 23 cases and in 6 malignant and 6 benign salivary gland tumors. The immunoreactivity of MMP-2 protein and MMP-2/TIMP-1, 2 ratio were significantly higher in active pleomorphic adenoma than in common pleomorphic adenoma (P = 0.028, P = 0.009, P = 0.045). The expression of active MMP-2, proMMP-9 and active MMP-9 were significantly higher in active pleomorphic adenoma than in common pleomorphic adenoma (P = 0.034, P = 0.021, P = 0.001). There was no significant difference in expression of MMP-2, MMP-9, TIMP-1 and TIMP-2 between the salivary malignant tumor and active pleomorphic adenoma, also between the salivary benign tumor and common pleomorphic adenoma. The expression of MMPs and TIMPs in active pleomorphic adenoma is similar to that in salivary carcinomas, and the expression in common pleomorphic adenoma also resembled to that in salivary adenoma. The expression of MMP-2, 9 and TIMP-1, 2 is related to the biological behavior of pleomorphic adenoma of salivary gland.

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Expression of Matrix Metalloproteinase (MMP)-2 and MMP-9 in Human Placenta and Fetal Membranes in Relation to Preterm and Term Labor

Extensive extracellular matrix (ECM) remodeling is found in many processes during human parturition at term and preterm. These include cervical ripening, fetal membrane rupture, and placental detachment from the maternal uterus. Matrix metalloproteinases (MMPs) are the main mediators of ECM degradation. The present study was designed to investigate the expression of MMP-2 and MMP-9 in human fetal membranes (FMs) and placental (PL) tissues with or without labor at preterm and term parturition. Both zymography and Western blot analysis showed that MMP-9 was significantly (P < 0.01) increased in preterm and term labor FM, compared with nonlabor. Term labor PL also had a much higher (P < 0.05) level of MMP-9 than that of term nonlabor. No significant difference in MMP-2 expression was found between labor and nonlabor tissues. Immunolocalization studies revealed a specific distribution pattern for MMP-2 and MMP-9. MMP-2 was localized to the amnion mesenchyme, chorion laeve trophoblast, decidua parietalis, and blood vessels in PL villi. MMP-9 was localized mainly to amnion epithelia, chorion laeve trophoblast, decidua parietalis, and PL syncytiotrophoblasts. Separate cell culture from different layers of FM and culture of purified PL trophoblast cells showed that PL syncytiotrophoblast and amnion epithelial cells exclusively produced MMP-9; chorion trophoblast cells secreted both MMP-2 and MMP-9, but amnion mesenchymal cells produced only MMP-2. We concluded that MMP-2 and MMP-9 exhibited cell-specific expression in the human PL. An increase in MMP-9 expression may contribute to degradation of the ECM in the FM and PL, thereby facilitating FM rupture and PL detachment from the maternal uterus at labor, both preterm and term.

Expression of matrix metalloproteinase (MMP)-2 and MMP-9 in human placenta and fetal membranes in relation to preterm and term labor.

Extensive extracellular matrix (ECM) remodeling is found in many processes during human parturition at term and preterm. These include cervical ripening, fetal membrane rupture, and placental detachment from the maternal uterus. Matrix metalloproteinases (MMPs) are the main mediators of ECM degradation. The present study was designed to investigate the expression of MMP-2 and MMP-9 in human fetal membranes (FMs) and placental (PL) tissues with or without labor at preterm and term parturition. Both zymography and Western blot analysis showed that MMP-9 was significantly (P < 0.01) increased in preterm and term labor FM, compared with nonlabor. Term labor PL also had a much higher (P < 0.05) level of MMP-9 than that of term nonlabor. No significant difference in MMP-2 expression was found between labor and nonlabor tissues. Immunolocalization studies revealed a specific distribution pattern for MMP-2 and MMP-9. MMP-2 was localized to the amnion mesenchyme, chorion laeve trophoblast, decidua parietalis, and blood vessels in PL villi. MMP-9 was localized mainly to amnion epithelia, chorion laeve trophoblast, decidua parietalis, and PL syncytiotrophoblasts. Separate cell culture from different layers of FM and culture of purified PL trophoblast cells showed that PL syncytiotrophoblast and amnion epithelial cells exclusively produced MMP-9; chorion trophoblast cells secreted both MMP-2 and MMP-9, but amnion mesenchymal cells produced only MMP-2. We concluded that MMP-2 and MMP-9 exhibited cell-specific expression in the human PL. An increase in MMP-9 expression may contribute to degradation of the ECM in the FM and PL, thereby facilitating FM rupture and PL detachment from the maternal uterus at labor, both preterm and term.