OBJECTIVETo evaluate the significance of the expression of matrix metalloproteinases (MMPs) in prostate cancer (PCa) and its clinical association.

METHODSFifty one cases of PCa and 10 cases of BPH were studied by immunohistochemical method using monoclonal antibodies to MMP2 and MMP9.

RESULTSThere was significant correlation between MMP2 or MMP9 and pathological grade, Gleason score and PCa metastasis.

CONCLUSIONThe expression of MMP2 and MMP9 may play an important role in the development and metastasis of PCa.

Aged ; Humans ; Immunohistochemistry ; Male ; Matrix Metalloproteinase 2 ; biosynthesis ; Matrix Metalloproteinase 9 ; biosynthesis ; Middle Aged ; Neoplasm Metastasis ; Prostatic Neoplasms ; metabolism ; pathology

BACKGROUND: We investigated the expression of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in malignant fibrous histiocytoma (MFH), and determined whether these could be useful as prognostic factors. METHODS: Among patients treated from 1993 to 2007, 30 cases of MFH were evaluated. Immunohistochemical staining was performed for MMP-2, MMP-9, TIMP-1, and TIMP-2 using paraffin wax-embedded blocks of MFH tissues. Reverse transcriptase polymerase chain reaction (RT-PCR) and Western blot and zymography were performed using fresh tissues obtained from 17 of the 30 cases. The levels of MMP and TIMP expression were compared between the MFH and normal control groups, and between non-metastatic and metastatic MFH groups. RESULTS: Expression levels of MMP-2, MMP-9, TIMP-1, and TIMP-2 were higher in the MFH group than the control group by RT-PCR, Western blotting, and zymography. Immunohistochemical staining revealed that MMP-2 and MMP-9 protein expression was higher in the metastatic than in the non-metastatic group. The expression levels of MMP-2 and TIMP-1 were significantly higher in the metastatic than in the non-metastatic group (p < 0.05) by RT-PCR. By Western blot analysis, the expression levels of MMP-2, TIMP-1, and TIMP-2 were higher in the metastatic group (p < 0.05), but MMP-9 showed only a slight increase in the metastatic group compared with the non-metastatic group (p > 0.05). Finally, gelatin zymography analysis showed that the expression levels of the pro- and active forms of MMP-2 were significantly higher in the metastatic group (p < 0.05), but the expression of the pro- and active forms of MMP-9 showed a slight decrease in the metastatic group (p > 0.05). CONCLUSIONS: These results suggest that MMP-2, MMP-9, TIMP-1, and TIMP-2 may have important roles in the development and progression of MFH, and that the degree of expression of these metalloproteinases and their inhibitors, especially MMP-2, could be useful as prognostic factors related to metastasis in MFH.
Adult ; Aged ; Aged, 80 and over ; Female ; Histiocytoma, Malignant Fibrous/*metabolism ; Humans ; Immunohistochemistry ; Male ; Matrix Metalloproteinase 2/*biosynthesis ; Matrix Metalloproteinase 9/*biosynthesis ; Middle Aged ; Neoplasm Metastasis ; Prognosis ; Tissue Inhibitor of Metalloproteinase-1/*biosynthesis ; Tissue Inhibitor of Metalloproteinase-2/*biosynthesis

OBJECTIVETo investigate the effects of angiotensin II (AngII) receptor (AT(1), AT(2)) antagonists on myocardial matrix metalloproteinases (MMPs) and fibronectin (FN) in rats with myocardial infarction (MI).

METHODSRat MI was induced by permanent ligation of the left coronary artery. Placebo, AT(1) receptor antagonist valsartan (10 mgxkg(-1)xd(-1)) or AT(2) receptor antagonist PD123319 (30 mgxkg(-1)xd(-1)) were given 7 days prior MI surgery. On the 1st, 3rd and 7th day after MI, Expressions of MMP-2, 3, 9, tissue inhibitors of matrix metalloproteinase-1 (TIMP-1) and FN at protein level were determined by Western blot in left ventricular free wall (LVFW), interventricular septum (IS) and right ventricular (RV). Myocardial FN distribution was also assayed by immunofluorescence.

RESULTSTypical myocardial remodeling was shown in IS and LVFW 7 days after MI. MMP-2, 3, 9 expressions at protein level were significantly increased whereas TIMP-1 and FN expressions significantly decreased in IS 1, 3, 7 days post MI in a time-dependent manner compared to that of sham operated hearts. MMP-2, 3, 9 expressions was significantly increased and TIMP-1 and FN expression significantly decreased in LVFW at the 1st post MI day and maintained up to 7th post MI day compared to that of sham operated hearts. Up-regulated expressions of MMP-2, 3, 9 and down-regulated TIMP-1 and FN expressions in IS and LVFW could be significantly attenuated by valsartan but not by PD123319. Valsartan but not PD123319 also significantly reduced MI sizes (40.4% +/- 2.1% vs 49.5% +/- 2.1%, P < 0.05).

CONCLUSIONAT(1) receptor antagonist involves in the pathology procession of myocardial remodeling and might lead to the development and progression of congestive heart failure by the increasing expressions of MMP-2, 3, 9, which contribute to degradative extracellular matrix FN in myocardium.

Angiotensin II Type 1 Receptor Blockers ; therapeutic use ; Animals ; Fibronectins ; biosynthesis ; Male ; Matrix Metalloproteinase 2 ; biosynthesis ; Matrix Metalloproteinase 3 ; biosynthesis ; Matrix Metalloproteinase 9 ; biosynthesis ; Myocardial Infarction ; drug therapy ; pathology ; Rats ; Rats, Wistar

To study the expression of matrix metalloproteinase-2 and -9 in human prostate cancer, matrix metalloproteinase-2 and -9 were immunohistochemically detected in tissues of prostate cancer and benign prostatic hyperplasia (BPH). Our results showed that matrix metalloproteinase-2 and -9 levels in prostate cancer were much higher than those in tissues of BPH, with the cancer invasion being positively correlated with the expression of the metalloproteinases. It is concluded that matrix metalloproteinase-2 and -9 are better molecular markers, which are of help in the diagnosis and prediction of prognosis of prostate cancer.
Humans ; Immunohistochemistry ; Male ; Matrix Metalloproteinase 2 ; biosynthesis ; genetics ; Matrix Metalloproteinase 9 ; biosynthesis ; genetics ; Neoplasm Invasiveness ; Prostatic Hyperplasia ; metabolism ; pathology ; Prostatic Neoplasms ; metabolism ; pathology

OBJECTIVETo investigate the correlation between type IV collagenase expression and metastatic potential of human prostate carcinoma cells.

METHODSHuman prostate carcinoma cell lines (LNCaP and C4-2B) with different metastatic potentials were selected. Using SABC immunocytochemical staining and zymographic analysis, we detected the difference of type IV collagenase expression and activity between the two cell lines.

RESULTSThe expression of type IV collagenase (MMP-2, MMP-9) could be detected in both LNCaP and C4-2B, mainly in cytoplasm, much higher in C4-2B than in LNCaP (P < 0.01). The activities of type IV collagenase in the conditioned medium of prostatic carcinoma cell LNCaP was the lowest, and the quantitative estimation values of MMP-2 and MMP-9 were 0.89 +/- 0.02 and 0.86 +/- 0.01, respectively. However, the quantitative estimation values of MMP-2 and MMP-9 in the conditioned medium of C4-2B were 96.32 +/- 4.36 and 33.89 +/- 1.84, respectively. Compared with LNCaP, the activity of type IV collagenase in C4-2B was much higher (P < 0.01).

CONCLUSIONCompared with LNCaP, the higher production capability of type IV collagenase in C4-2B may possibly contribute to its invasive and metastatic potentials. The expression of type IV collagenase of human prostate carcinoma cells is closely correlated to the metastatic and invasive potential.

Cell Line, Tumor ; Humans ; Male ; Matrix Metalloproteinase 2 ; biosynthesis ; metabolism ; Matrix Metalloproteinase 9 ; biosynthesis ; metabolism ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Prostatic Neoplasms ; enzymology ; pathology

OBJECTIVE: To determine the effect of progesterone on the secretion of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) in ectopic endometrial stromal cells. METHODS: Ectopic endometrial stromal cells were obtained from 17 patients with endometriosis. Endometrial stromal cells were obtained from 12 patients with endometriosis and 14 cases of controls. Ectopic endometrial stromal cells of 15 cases were treated with progesterone. Culture supernatants of these stromal cells were analyzed for MMP-2 and MMP-9 by zymography. RESULTS: Endometriotic stromal cells released significantly higher levels of MMP-2 and MMP-9 than endometrial stromal cells from women with and without endometriosis. Progesterone at 10(-9) mol/L caused endometriotic stromal cells a significant reduction MMP-2 and MMP-9 levels. When progesterone concentration was increased from 10(-9) mol/L to 10(-7) mol/L, the release of MMP-9 was almost completely inhibited, wherease that of MMP-2 was not completely inhibited. CONCLUSION Progesterone may inhibit the secretion of MMP-2 and MMP-9 in ectopic endometrial stromal cells, especially MMP-9.
Adult ; Endometriosis ; metabolism ; pathology ; Endometrium ; metabolism ; pathology ; Female ; Humans ; Matrix Metalloproteinase 2 ; biosynthesis ; genetics ; Matrix Metalloproteinase 9 ; biosynthesis ; genetics ; Progesterone ; pharmacology ; Stromal Cells ; metabolism

OBJECTIVETo investigate the effects of E-cadherin on the biologic behavior of SUM149, an inflammatory breast cancer cell line.

METHODSSUM149 cells were transfected with dominant-negative mutant E-cadherin expressing plasmid. The positive clones with higher expression of dominant-negative E-cadherin mutant were identified by RT-PCR and fluorescent flow cytometry method. The differences in cell growth, proliferation and invasion between positive clones and controls were compared.

RESULTSWhereas the proliferation of positive clones was of no change, compared with controls, the ability of invasion was decreased and the mRNA levels of MMP-1 and MMP-9 were downregulated. Gelatin zymography analysis also confirmed the decreasing expression of MMP-9 in the positive clones.

CONCLUSIONIn this cell line model, down-regulation of E-cadherin can inhibit the ability of invasion of this inflammatory breast cancer cell line.

Breast Neoplasms ; metabolism ; pathology ; Cadherins ; biosynthesis ; genetics ; physiology ; Cell Line, Tumor ; Down-Regulation ; Female ; Humans ; Matrix Metalloproteinase 1 ; biosynthesis ; genetics ; Matrix Metalloproteinase 9 ; biosynthesis ; genetics ; Mutation ; Neoplasm Invasiveness ; Plasmids ; RNA, Messenger ; biosynthesis ; genetics ; Transfection

UNLABELLEDTo investigate the expressions of fibrillin-1, elastin and matrix metalloproteinase-1 and -9 (MMP-1, 9) in chronic actinic dermatitis in elderly patients and explore the pathogenesis of the disease.

METHODSTwenty-three patients with chronic actinic dermatitis were examined for the expressions of fibrillin-1, elastin, MMP-1, and MMP-9 with immunohistochemistry in the skin lesions. Image analysis was carried out to measure MMP-1 and MMP-9 expressions semi-quantitatively.

RESULTSIn the skin lesions of patients with chronic actinic dermatitis, elastin expression was obviously reduced or absent in the papillary dermis. The elastic fibers were disorderly arranged in the reticular dermis with local aggregation in some regions. Obvious fibrillin-1 deposition was found in the reticular dermis. Increased expressions of MMP-1, but not that of MMP-9, was found in the skin lesions of the patients.

CONCLUSIONElastin and fibrillin-1 deposition can be found in the skin lesions in patients with chronic actinic dermatitis, suggesting the association of increased MMP-1 expression with the elastic tissue degeneration in the lesions. MMP-9 does not exhibit an obvious association with the pathogenesis of chronic actinic dermatitis in elderly patients.

Aged ; Elastin ; biosynthesis ; Female ; Fibrillin-1 ; Fibrillins ; Humans ; Immunohistochemistry ; Male ; Matrix Metalloproteinase 1 ; biosynthesis ; Matrix Metalloproteinase 9 ; biosynthesis ; Microfilament Proteins ; biosynthesis ; Middle Aged ; Photosensitivity Disorders ; etiology ; metabolism ; Sunlight ; adverse effects

In order to investigate the relationship between VEGF and matrix metalloproteinase (MMP)-2, -9 in acute myeloid leukemia patients, and evaluate the significance of them in extramedullary leukemic invasion, the expressions of MMP-2 mRNA, MMP-9 mRNA, VEGF mRNA in bone marrow from 86 patients with acute myeloid leukemia (AML), as well as human hematopoietic cell lines were analyzed by reverse transcription-polymerase chain reaction (RT-PCR). The proteolytic activities of MMP-2 and MMP-9 in the supernatants were measured by zymography. The VEGF protein in serum of all samples was detected by ELISA. All these results were analyzed for determination of the relationship between VEGF and MMP-2, MMP-9. The results showed that there was a positive correlation between expressions of MMP-2 mRNA or MMP-9 mRNA and VEGF mRNA or protein. But no such correlation was demonstrated in the AML (CR) and normal control (NC) groups. A higher expression level of MMP-2 and MMP-9 in the VEGF positive group was found, as compared with the negative group (P < 0.05). More extramedullary infiltration occurred in VEGF positive groups than that in VEGF negative groups of AML. The expression of bcl-2 in HL-60 cells was upregulated by VEGF. It is concluded that there are significantly positive correlations between the expression of MMP-2 and MMP-9 with VEGF mRNA or protein levels in AML patients. VEGF can upregulate the expression of MMP-2, MMP-9 in HL-60 and a part of the primary leukemic cells. VEGF and MMP-2, MMP-9 may participate in the extramedullary leukemic invasion of AML patients.
Adolescent ; Adult ; Aged ; Female ; HL-60 Cells ; Humans ; Leukemia, Myeloid, Acute ; metabolism ; pathology ; Leukemic Infiltration ; Male ; Matrix Metalloproteinase 2 ; biosynthesis ; genetics ; Matrix Metalloproteinase 9 ; biosynthesis ; genetics ; Middle Aged ; RNA, Messenger ; biosynthesis ; genetics ; Vascular Endothelial Growth Factor A ; biosynthesis ; genetics

To investigate the expression of NF-kappaB in acute leukemia and its relationship with P21, and matrix metalloproteinases (MMP), the expression of NF-kappaB, P21, MMP-2 and MMP-9 in bone marrow cells from patients with acute leukemia (AL) was detected using immunocytochemical technique. The results showed that the expression ratios of NF-kappaB, P21, MMP-2 and MMP-9 in untreated AL group were significantly higher than those in remission and normal control groups (P < 0.05), and no obvious difference was seen between remission and normal control groups. The expression of NF-kappaB was correlated with that of P21, MMP-2 and MMP-9 (r = 0.767, 0.729 and 0.803, respectively, P < 0.05). This study indicated that P21 protein, encoded by oncogene Ras, and NF-kappaB were super-expressed in leukemia cells. In conclusion, after activation by Ras, NF-kappaB combined with the kappaB sequences of MMP-2 and MMP-9 genes, then upregulated their expression. MMP might enhance the degradative function of leukemic cell, thus to make cells easier to cross through the bone marrow barrier and release into blood.
Acute Disease ; Adult ; Bone Marrow Cells ; metabolism ; Female ; Humans ; Immunohistochemistry ; Leukemia ; drug therapy ; metabolism ; pathology ; Male ; Matrix Metalloproteinase 2 ; biosynthesis ; Matrix Metalloproteinase 9 ; biosynthesis ; NF-kappa B ; biosynthesis ; Proto-Oncogene Proteins p21(ras) ; biosynthesis ; Remission Induction