No abstract available.
Matrix Metalloproteinases* ; Stomach Neoplasms ; Tissue Inhibitor of Metalloproteinase-1 ; Tissue Inhibitor of Metalloproteinase-2

BACKGROUND : Tumor invasion and metastasis are the major causes of morbidity and death for cancer patients. Metastasis is a complex multistep process in which tumor cells must pass through supporting structures. Proteolytic degradation of the structures is an important part of this process, and matrix metalloproteinase (MMP) has been implicated. The activation and the enzymatic activity of MMP is regulated by the tissue inhibitor metalloproteinase (TIMP). Three distinct TIMP molecules have been isolated. Very little is known about the role of TIMP-2 in tumors. The purpose of this study was to examine the expression of TIMP-2 in human colorectal carcinomas. METHODS : The paraffin blocks of 33 colorectal carcinomas were recalled and immunostained with monoclonal antibodies specific for TIMP-2. The rate of stain was estimated, and the relationships between the expression and the stage, the differentiation, and the recurrence were assessed. RESULTS : The expression of TIMP-2 in tumor tissues increased with increasing Dukes's stage (p<0.05) and recurred cases (p<0.05). CONCLUSIONS : Our results suggest that increased expression of TIMP-2 may be useful as a marker of biologic aggressiveness.
Antibodies, Monoclonal ; Colorectal Neoplasms* ; Humans* ; Matrix Metalloproteinase 2* ; Neoplasm Metastasis ; Paraffin ; Recurrence ; Tissue Inhibitor of Metalloproteinase-2

OBJECTIVETo explore the invasiveness of xenografts on chicken embryo chorioallantoic membrane (CAM) after tissue inhibitor of metalloproteinase-2 (TIMP-2) gene transfection.

METHODSFresh ameloblastoma tissues were minced into 1-2 mm3 and transplanted on the CAM. There were three groups named as control group (Empt), plasma transfection group (Lipo), and TIMP-2 gene transfection group (P). The specimens were respectively investigated by microscope indifferent spots after implanting. The volume of the xenografts and the weight of xenografts in the termination time of the experiment were recorded. The invasiveness of xenografts was divided into four grades by pathological examination. Western blot analysis was performed to investigate matrix metalloproteinase-2 (MIMP-2) and TIMP-2 protein in xenografts.

RESULTSAmeloblastoma tissues can survive on CAM and the tumor cells may invade it on 5-7 days after implanting. At 9 d after implanting, the invasiveness grades in P group were 7 in grade 0, 1 in grade 2, 0 in grade 3. The expression of TIMP-2 protein in P group was significantly higher than that in Empt group (P < 0.05). The expression of MMP-2 protein in P group was lower than that in Empt group (P < 0.05).

CONCLUSIONThe xenotransplanted tumor model of human ameloblastoma on CAM was successfully established. The invasiveness of ameloblastoma xenografts was suppressed might be due to TIMP-2 gene transfection.

Ameloblastoma ; Animals ; Chickens ; Chorioallantoic Membrane ; Heterografts ; Humans ; Matrix Metalloproteinase 2 ; Tissue Inhibitor of Metalloproteinase-2 ; Transfection

OBJECTIVETo detect protein expression of MMPs and TIMPs in various salivary gland neoplasms and to investigate their roles in invasion and metastasis of the malignant salivary gland tumors.

METHODSImmunohistochemistry and Gelatin zymography analyses for MMP-2, MMP-9, MT1-MMP, TIMP-1 and TIMP-2 were performed in 26 malignant and 28 benign salivary gland tumors.

RESULTSThe expression of MMP-2 and MMP-9 was significantly higher in carcinomas than in adenomas (P < 0.05). The MMP-2/TIMP-1 and MMP-2/TIMP-2 was also significantly higher in carcinomas than in adenomas (P < 0.05). There was a cooperated effect among MMP-2, MT1-MMP and TIMP-2. The expression of active MMP-2, proMMP-9 and active MMP-9 was significantly higher in malignant tumors than in benign tumors (P < 0.05).

CONCLUSIONMMP-2 and MMP-9 may play important roles in invasion of malignant salivary gland tumors. A disturbed balance between MMP-2, MMP-9, TIMP-1 and TIMP-2 in malignant salivary gland tumors was detected. It was the absolute increase of MMP-2 and MMP-9 to induce the unbalance.

Enzyme Precursors ; Humans ; Immunohistochemistry ; Matrix Metalloproteinase 2 ; Matrix Metalloproteinase 9 ; Matrix Metalloproteinases ; Salivary Gland Neoplasms ; Salivary Glands ; Tissue Inhibitor of Metalloproteinase-1 ; Tissue Inhibitor of Metalloproteinase-2

Matrix metalloproteinases (MMPs) and their inhibitors (tissue inhibitors of matrix metalloproteinases, TIMPs) play essential roles in the remodelling of the extracellular matrix. The balance between MMPs and TIMPs is altered in neoplasia, contributing to the invasive and metastatic properties of malignant tumors. Although MMP and TIMP are believed to play an important role in invasion and metastasis in malignant solid tumors, little is known about their involvement in malignant lymphoma. Immunohistochemical stains for MMP-1, MMP-2, MMP-9, TIMP-1 and TIMP-2 were performed using 56 paraffin blocks of the malignant lymphoma and the results were analyzed by using the tumor grade by Working Formulation. The expression of MMP-9 was noted in 45.5% of low grade, 86.1% of intermediate grade, and 100% of high grade malignant lymphoma. The incidence of MMP-9 expression in tumor cells was positively correlated with the grade of the malignant lymphoma (P<0.025). In nodal lymphomas, the incidence of the MMP-9 expression of the tumor cells was higher in malignant lymphoma with extracapsular invasion than those without extracapsular invasion (P=0.008). The incidence of TIMP-1 expression in the tumor cells and fibroblasts was positively correlated with the grade of the malignant lymphoma (P<0.025). In nodal lymphoma, the incidence of the TIMP-1 expression of the tumor cells was higher in malignant lymphoma with extracapsular invasion than those without extracapsular invasion (P=0.009). The incidences of the MMP-1, MMP-2, and TIMP-2 expression in malignant lymphoma were neither increased in the malignant lymphoma with extracapsular tumor invasion nor correlated with the grade by working formulation. There was no significant difference in the expression rate of MMP-1, MMP-2, MMP-9, TIMP-1, and TIMP-2 in nodal- and extra-nodal malignant lymphoma. The above results suggest that the expressions of MMP-9 and TIMP-1 are positively correlated with the grade and the presence of extranodal tumor invasion in malignant lymphomas.
Coloring Agents ; Extracellular Matrix ; Fibroblasts ; Incidence ; Lymphoma* ; Matrix Metalloproteinases ; Neoplasm Metastasis ; Paraffin ; Tissue Inhibitor of Metalloproteinase-1 ; Tissue Inhibitor of Metalloproteinase-2

BACKGROUND: MMPs and TIMPs are important factors for abnormal remodeling the pulmonary parenchyme in idiopathic interstitial pneumonia(IIP) This study evaluated the expression of MMPs and TIMPs in the tissue of IPF, NSIP and normal control subjects. METHOD: The MMP-2 and -9 activity in the lung tissue was studied by gelatin zymography, and the expression of MMP-1, -2 ,-9, TIMP-1 and -2 in the lung tissue was measured by immunohistochemistry. Thirty five patients, who were diagnosed with IIP (UIP ; 22, NSIP ; 13), were enrolled in the immunohistochemical study. Thirteen patients with IIP (UIP ; 9, NSIP ; 4) and five patients with lung cancer were enrolled in the zymographic assay. RESULTS: (1) The immunohistochemistry for MMP-1,-2,-9, TIMP-1 and-2 ; MMP-1,-9 and TIMP-2 were stained stronger in the UIP subjects than NSIP and the normal control. TIMP-2 was strongly stained in the UIP tissue. particularly the fibroblasts in the fibroblastic foci. (2) Zymography for MMP-2 and MMP-9 revealed MMP-2 to have prominent expression in the UIP tissue than in the NSIP tissue. CONCLUSIONS: These results suggest that the overexpression of the TIMPs and gelatinases in UIP might be? important factors in the irreversible fibrosis of the lung parenchyme.
Fibroblasts ; Fibrosis ; Gelatin ; Gelatinases ; Humans ; Immunohistochemistry ; Lung ; Lung Neoplasms ; Matrix Metalloproteinases* ; Tissue Inhibitor of Metalloproteinase-1 ; Tissue Inhibitor of Metalloproteinase-2

BACKGROUND: Matrix metalloproteinases (MMPs) have been implicated in the remodelling of extracellular matrix (ECM), including basement membrane. ECM remodelling is associated with pathological processes, including hepatic fibrosis, tumor invasion and metastasis. Tissue inhibitors of metalloproteinase (TIMP)-1 and TIMP-2 were known to inhibit MMP-9 and MMP-2, respectively. In the present study, we examined the expression of TIMP-1 and TIMP-2 in surgical specimen pairs of hepatocellular carcinoma and nontumoral liver and the correlation between their expression and clinicopathological characteristics. METHODS: The localization of both transcripts and protein of TIMP-1 and TIMP-2 was studied by using in situ hybridization and immunohistochemistry. RESULTS: TIMP-1 and TIMP-2 mRNA transcripts were found in tumor cells, hepatocyte, sinusoidal cells, endothelial cells and stromal cells. Signal intensity of TIMP-1 was stronger than that of TIMP-2. The results of immunohistochemical stainings were concordant with those obtained by in situ hybridization. Expression of TIMP-1 and TIMP-2 was observed in tumorous tissue, in nontumorous tissue and in the portions of the tumors adjacent to the capsules. However, a clear difference in TIMP-1 and TIMP-2 mRNA expression was not observed among the three tissue types. The intensity of TIMP-2 expression was generally weaker than that of TIMP-1, and the intensity of TIMP-1 and TIMP-2 mRNA expression did not correlate with variable clinicopathological characteristics. CONCLUSION: TIMPs was expressed in tumor cells and many cell types of the nontumoral liver. Further investigations for TIMPs' unknown functional role are needed.
Adult ; Aged ; Carcinoma, Hepatocellular/pathology ; Carcinoma, Hepatocellular/metabolism* ; Female ; Human ; Immunohistochemistry ; Liver Neoplasms/pathology ; Liver Neoplasms/metabolism* ; Male ; Middle Age ; RNA, Messenger/analysis ; Tissue Inhibitor-of Metalloproteinase-2/physiology ; Tissue Inhibitor-of Metalloproteinase-2/genetics* ; Tissue Inhibitor-of Metalloproteinase-2/analysis ; Tissue-Inhibitor of Metalloproteinase-1/physiology ; Tissue-Inhibitor of Metalloproteinase-1/genetics* ; Tissue-Inhibitor of Metalloproteinase-1/analysis

PURPOSE: We investigated the extent of adenosine A1 agonist-induced expression and regulation of matrix metalloproteinase 2 (MMP-2) synthesis in human trabecular meshwork cells (HTMC). METHODS: Primary HTMC cultures were exposed to 0.1 or 1.0 µM N6-cyclohexyladenosine (CHA) for 2 h in the presence or absence of an inhibitor thereof, 8-cyclopentyl-1,3-dimethylxanthine (CPT). The expression level of mRNA encoding MMP-2 was assessed via reverse transcription-polymerase chain reaction, and the levels of tissue inhibitor of metalloproteinase 2 (TIMP2) and membrane-type-1 MMP (MT1-MMP) measured by Western blotting. The permeability of the HTMC monolayer was assessed with the aid of carboxyfluorescein. RESULTS: CHA at 1.0 µM increased the permeability of the HTMC monolayer (p = 0.003) and CHA at both 0.1 and 1.0 µM significantly increased MMP-2 mRNA expression, which was inhibited by co-exposure to CPT (all p < 0.05). CHA increased MMP-2 activity, decreased that of TIMP2, and increased that of MT1-MMP (all p < 0.05). CONCLUSIONS: CHA increased the permeability of the HTMC monolayer and increased MMP-2 activity, decreased TIMP2 activity, and increased MT1-MMP activity. Thus, regulation of TIMP2 and MT1-MMP expression may be involved in the adenosine A1 agonist-induced increase in MMP-2 activity.
Adenosine ; Blotting, Western ; Humans ; Matrix Metalloproteinase 14 ; Matrix Metalloproteinase 2 ; Permeability ; RNA, Messenger ; Tissue Inhibitor of Metalloproteinase-2 ; Trabecular Meshwork

BACKGROUND: In the idiopathic interstitial pneumonia (IIP), it has been known that imbalance between matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) is important factor for abnormal remodeling of lung parenchyme. This study was performed to compare the expression of MMPs and TIMPs in the normal subjects and patients with IIP. METHODS: Seventeen patients were diagnosed as IIP by open lung biopsy (male: female 7:10) and four patients as normal control were diagnosed as lung cancer and treated by lobectomy or pneumonectomy from March, 1999 to August 2001 at Gil medical center. IIP group divided into UIP (n=10) and NSIP (n=7). MMP-1 and TIMP-2 of their lung tissue were stained by immunohistochemical method and were graded 4 levels (grage 0-3) following stained status. RESULTS: MMP-1 was stained more strongly in the IIP than normal. But it had no differences between UIP and NSIP. TIMP-1 and-2 were stained more strongly in the UIP than NSIP but not stained in the normal. In the UIP, TIMP-2 was stained strongly in fibroblast foci. CONCLUSION: These results suggst that imbalance between MMPs and TIMPs may be important factor of pathogenesis of pulmonary fibrosis in the IIP. It is thought that major site of TIMP-2 is myofibroblast in the fibroblast foci.
Biopsy ; Female ; Fibroblasts ; Humans ; Idiopathic Interstitial Pneumonias* ; Lung ; Lung Neoplasms ; Matrix Metalloproteinase 1* ; Matrix Metalloproteinases ; Metalloproteases ; Myofibroblasts ; Pneumonectomy ; Pulmonary Fibrosis ; Tissue Inhibitor of Metalloproteinase-1 ; Tissue Inhibitor of Metalloproteinase-2

STUDY DESIGN: The serum levels of transforming growth factor-beta 1 (TGF-beta1), tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) and TIMP-2 were measured by enzyme-linked immunosorbent assay. PURPOSE: To compare the serum levels of TGF-beta1, TIMP-1 and TIMP-2 between patients with lumbar spinal stenosis and disc herniation. OVERVIEW OF LITERATURE: It has been reported that increased concentrations of TGF-beta1, TIMP-1 and TIMP-2 in the ligamentum flavum might be a possible pathogenesis for ligamentum flavum hypertrophy in spinal stenosis. However, it is not determined whether this phenomenon in spinal stenosis is a local or systemic problem. METHODS: The concentrations of TGF-beta1, TIMP-1 and TIMP-2 were quantitatively analyzed by ELISA in the ligamentum flavum and serum of patients with lumbar spinal stenosis (n=16) and disc herniation (n=16). The thickness of ligamentum flavum was measured on axial T1-weigted magnetic resonance image. The biochemical and radiological results were compared for the two conditions. RESULTS: The thickness of the ligamentum flavum was larger in patients with spinal stenosis compared with that with disc herniation (p=0.001). The mean concentrations of TGF-beta1, TIMP-1, and TIMP-2 in the ligamentum flavum were significantly higher in patients with spinal stenosis than those with disc herniation (all, p < 0.05). However, the difference in serum levels of TGF-beta1 (p=0.464), TIMP-1 (p=0.146) and TIMP-2 (p=0.794) was not significant between the lumbar spinal stenosis and disc herniation patients. CONCLUSIONS: Despite increased levels of TGF-beta1, TIMP-1, and TIMP-2 in the ligamentum flavum of spinal stenosis patients compared to disc herniation patients, the serum levels of TGF-beta1, TIMP-1 and TIMP-2 were very similar in both groups. These results indicate that the role of TGF-beta1, TIMP-1 and TIMP-2 on hypertrophy of the ligamentum flavum in spinal stenosis patients is a local phenomenon, not systemic.
Enzyme-Linked Immunosorbent Assay ; Humans ; Hypertrophy ; Ligamentum Flavum ; Matrix Metalloproteinase 1 ; Spinal Stenosis* ; Tissue Inhibitor of Metalloproteinase-1* ; Tissue Inhibitor of Metalloproteinase-2* ; Transforming Growth Factor beta1*