MAB13431 Sigma-AldrichAnti-MMP-2 Antibody, pro and active form, clone A-Gel VC2

Migration of the smooth muscle cells (SMCs) to the tunica media in the saphenous vein (SV) transplants is facilitated by matrix metalloproteinases (MMPs). The aim of this study was to identify any associations between expression of MMP-2 or endogenous tissue inhibitors (TIMP-2 and TIMP-3) in the SV segments and late failure of the SV grafts.Two hundred consecutive patients with a mean age of 63.1 ± 8.9 years who underwent primary isolated venous CABG were examined. Patients were retrospectively split into two subgroups, with the SV graft disease (SVGD (+); n = 47) or without it (SVGD (-); n = 153). In the SV segments, immunohistochemical analysis of the expression of the MMP-2, TIMP-2, and -3 was performed.In the SVGD (+) patients, tissue expression of MMP-2 was stronger, whereas that of both TIMPs was weaker than in the SVGD (-) patients. In majority of the SV segments obtained from the SVGD (-) individuals, a balance in MMP and TIMP expressions was found, whereas an upregulation of MMP-2 expression was usually noted in the SVGD (+) subjects.The strong expression of MMP-2 accompanied by reduced immunostaining of both TIMPs is associated with the development of the SV graft disease and unfavorable CABG outcomes.

Oligosaccharides aberrantly expressed on tumor cells influence processes such as cell adhesion and modulation of the cell's microenvironment resulting in an increased malignancy. Schmidt's imidate strategy offers an effective method to synthesize libraries of various oligosaccharide mimetics. With the aim to perturb interactions of tumor cells with extracellular matrix proteins and host cells, molecules with 3,4-bis(hydroxymethyl)furan as core structure were synthesized and screened in biological assays for their abilities to interfere in cell adhesion and other steps of the metastatic cascade, such as tumor-induced angiogenesis.The most active compound, (4-{[(β-D-galactopyranosyl)oxy]methyl}furan-3-yl)methyl hydrogen sulfate (GSF), inhibited the activation of matrix-metalloproteinase-2 (MMP-2) as well as migration of the human melanoma cells of the lines WM-115 and WM-266-4 in a two-dimensional migration assay. GSF inhibited completely the adhesion of WM-115 cells to the extracellular matrix (ECM) proteins, fibrinogen and fibronectin.In an in vitro angiogenesis assay with human endothelial cells, GSF very effectively inhibited endothelial tubule formation and sprouting of blood vessels, as well as the adhesion of endothelial cells to ECM proteins. GSF was not cytotoxic at biologically active concentrations; neither were 3,4-bis{[(β-D-galactopyranosyl)oxy]methyl}furan (BGF) nor methyl β-D-galactopyranoside nor 3,4-bis(hydroxymethyl)furan, which were used as controls, eliciting comparable biological activity. In silico modeling experiments, in which binding of GSF to the extracellular domain of the integrin α(v)β(3) was determined, revealed specific docking of GSF to the same binding site as the natural peptidic ligands of this integrin. The sulfate in the molecule coordinated with one manganese ion in the binding site.These studies show that this chemically easily accessible molecule GSF, synthesized in three steps from 3,4-bis(hydroxymethyl)furan and benzoylated galactose imidate, is nontoxic and antagonizes cell physiological processes in vitro that are important for the dissemination and growth of tumor cells in vivo.

Urothelial bladder carcinomas show a divergent biological behavior, which significantly complicates risk stratification and clinical management. The MMP repressor RECK and the MMP activator EMMPRIN regulate the invasive potential by metalloproteinase-induced stromal degradation. Data on RECK in urothelial bladder cancer are lacking and information on EMMPRIN is sparse. This study aims to investigate the expression of RECK and EMMPRIN in urothelial carcinoma of the bladder and to correlate these findings with clinicopathological parameters.Our study included 127 specimens of urothelial carcinomas derived from 103 patients who underwent either TUR-B or cystectomy. Immunohistochemical expression analysis was performed for RECK, EMMPRIN, MMP-2, MMP-9 and MMP-14. Expression levels were graded for staining intensity and correlated with pT stage and WHO tumor grade.Invasive (≥pT1) as well as WHO high-grade urothelial carcinomas showed a statistically significant and stepwise downregulation of RECK (p less than 0.001) and concomitant upregulation of EMMPRIN (p less than 0.001) compared to non-invasive and WHO low-grade tumors. No correlation was observed for the MMPs investigated.Decreased RECK and increased EMMPRIN expression are associated with increasing stage and grade. Both proteins may serve as molecular marker for the distinction between potentially invasive (≥pT1) and non-invasive tumors (≤pTa).

Prostate cancer is the most common cancer in men and second in the cancer-related frequency of mortality. Matrix metalloproteinases (MMPs) are involved in tumor invasion and metastasis in various malignancies. MMP-2 and MMP-9 are capable of digesting collagen type IV. Numerous studies have demonstrated an association between increased MMP-2 and -9 expression and tumor progression in various tumors. In this study, the expression and activities of MMP-2 and -9 were assessed in serum probes and tumor tissue from core needle biopsies and radical prostatectomies of 97 patients. MMP-2 and -9 serum expression was analyzed in a subgroup of 31 patients. MMP-9 serum expression was significantly increased in tumor patients and correlated with tumor grade. In contrast, the MMP-9 tissue expression and activity revealed no significant correlations to tumor stage or grade. The MMP-2 activity, however, showed a positive correlation for MMP-2 with tumor stage. Increased activity was predominantly detected in advanced tumor stages. Immunohistochemical analysis of MMP-2 expression demonstrated a positive association with tumor grade in prostatectomy specimens. The relative expression rates in biopsies matched in 65% with those of the prostatectomies. Detection of MMP-2 in core needle biopsies seems not to be a helpful marker for diagnostic purposes.