Reduced angiogenesis by marimastat in peritoneal dissemination model of gastric cancer

Wada, Norihito; Otani, Yoshihide; Kubota, Tetsuro; Kimata, Masaru; Minagawa, Akiko; Kumai, Koichiro; Kameyama, Kaori; Okada, Yasunori; Kitajima, Masaki

doi:10.1016/s0016-5085(00)85212-9

Cited by 6 publications

(7 citation statements)

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“…The principle introduced by Galis et al (1995) has been modified in the procedure to demonstrate breakdown of gelatin differently. Instead of fluorescent gelatin, some authors used pure gelatin that was stained after incubation with Ponceau S (Loy et al 2002), amido black (Ikeda et al 2000; Furuya et al 2001), or Biebrich Scarlet (Wada et al 2003). Another approach based on zymography was used by Kurschat et al (2002), who incorporated gelatin into polyacrylamide gels of 50 μm thickness, which were brought into contact with unfixed cryostat sections.…”

Section: In Situ Zymography Of Gelatinase Activitymentioning

confidence: 99%

Metabolic Mapping of Proteinase Activity with Emphasis on In Situ Zymography of Gelatinases

Frederiks

Mook

2004

J Histochem Cytochem.

111

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S U M M A R Y Proteases are essential for protein catabolism, regulation of a wide range of biological processes, and in the pathogenesis of many diseases. Several techniques are available to localize activity of proteases in tissue sections or cell preparations. For localization of the activity of matrix metalloproteinases, in situ zymography was introduced some decades ago. The procedure is based on zymography using SDS polyacrylamide gels containing gelatin, casein, or fibrin as substrate. For in situ zymography, either a photographic emulsion containing gelatin or a fluorescence-labeled proteinaceous macromolecular substrate is brought into contact with a tissue section or cell preparation. After incubation, enzymatic activity is revealed as white spots in a dark background or as black spots in a fluorescent background. However, this approach does not allow precise localization of proteinase activity because of limited sensitivity. A major improvement in sensitivity was achieved with the introduction of dye-quenched (DQ-)gelatin, which is gelatin that is heavily labeled with FITC molecules so that its fluorescence is quenched. After cleavage of DQ-gelatin by gelatinolytic activity, fluorescent peptides are produced that are visible against a weakly fluorescent background. The incubation with DQ-gelatin can be combined with simultaneous immunohistochemical detection of a protein on the same section. To draw valid conclusions from the findings with in situ zymography, specific inhibitors need to be used and the technique has to be combined with immunohistochemistry and zymography. In that case, in situ zymography provides data that extend our understanding of the role of specific proteinases in various physiological and pathological conditions.

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Section: In Situ Zymography Of Gelatinase Activitymentioning

confidence: 99%

Metabolic Mapping of Proteinase Activity with Emphasis on In Situ Zymography of Gelatinases

Frederiks

Mook

2004

J Histochem Cytochem.

111

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“…In addition, MMPs, particularly MMP2 and MMP9, are postulated to promote invasion and lymph node metastasis of gastrointestinal cancer cells. Suppression of MMP activity impairs cancer cell migration and angiogenesis 24–26…”

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confidence: 99%

Runx3 suppresses gastric cancer metastasis through inactivation of MMP9 by upregulation of TIMP‐1

Chen

Wei

Guo

et al. 2011

Intl Journal of Cancer

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Recent studies have suggested that loss of RUNX3 expression is involved with gastric tumor metastasis. However, the precise mechanism of RUNX3-mediated suppression of tumor metastasis remains elusive. We aimed to clarify the effect of RUNX3 on tumor metastasis in gastric cancer cell lines and tumors. Immunohistochemistry revealed that RUNX3 was significantly decreased in metastatic gastric cancer. Gelatin zymography and Western blot showed that instead of regulating matrix metalloproteinase 9 (MMP9) expression, RUNX3 expression inhibited MMP9 enzyme activity, and this was consistent with the upregulation of tissue inhibitor of metalloproteinases 1 (TIMP1) by RUNX3. TIMP1 siRNA treatment impaired RUNX3-mediated suppression of gastric cancer cell invasion. Reporter assays demonstrated regulation of TIMP-1 by RUNX3. Two RUNX3 binding sites were identified in the TIMP-1 promoter and direct interaction of RUNX3 with the TIMP-1 promoter was confirmed in vitro and in vivo. These findings provide evidence for RUNX3-mediated suppression of gastric cancer invasion and metastasis and define a novel molecular mechanism that for the metastasis-inhibiting activity of RUNX3. These data may be applied in the development of RUNX3 for gastric cancer metastasis diagnostics and therapeutics.Gastic cancer is second only to lung cancer as a cause of cancer-related deaths worldwide, and poor prognosis and high mortality continue to be problems with this disease. 1-3 Approximately 20% of patients survive to 5 years, 4 and metastasis is a major cause of mortality in gastric cancer patients. Clearly, improvements in treatment depend on understanding the molecular mechanisms of gastric cancer metastasis. In general, cancer metastasis consists of a series of sequential, interrelated events involving growth factors, cell-adhesion molecules, matrix-degradation enzymes and motility factors. These molecules induce not only cell growth but also the extracellular matrix (ECM) degradation and angiogenesis that are required for tumor invasion and proliferation. 5 Previous research on the molecular pathology of gastric cancer metastasis identified a variety of key oncogenes and tumor suppressor genes in this process, such as c-erbB2, c-met, p27 and pRb. [6][7][8][9][10][11] Recently, deficiency in the Runt-related gene RUNX, which is a candidate tumor suppressor, was found to be causally related with gastric cancer. 12 The RUNX family members, RUNX1, RUNX2 and RUNX3, encode DNA-binding a subunits that bind a common b subunit, CBFb, to generate heterodimeric transcription regulators. 13 All three RUNX family members play important roles in normal developmental processes and carcinogenesis. 14-18 Recent studies showed that RUNX3 expression levels are downregulated in gastric cancer, either from hemizygous deletion or from promoter methylation of the RUNX3 gene. Furthermore, a decrease in RUNX3 protein expression is significantly associated with decreased survival of gastric cancer patients. Li et al. 12 showed that RUNX3 expression was decreased in ...

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“…Both P2X7 and P2Y2 appear to be the major P2 receptors involved in this process, with well-established roles for various cell surface molecules including amyloid precursor protein, CD23, CD27 and CD62L, although a role for P2X7 in amyloid precursor protein shedding remains to be clearly defined. Importantly, a number of studies have shown that P2 receptor-mediated ectodomain shedding for some molecules, BB-2516 (marimastat) Metalloproteases (broadspectrum) [104] BB-3103 Metalloproteases (broadspectrum) [105] BB-94 (batimastat) Metalloproteases (broadspectrum) [106] Decanoyl-RVKR-CMK Convertase (non-selective) [107] GI 254023X ADAM10 [108] GM 6001 Metalloproteases (broadspectrum) [109] GW 280264X ADAM10 and ADAM17 [108] Phenanthroline Metalloproteases (broadspectrum) [ …”

Section: Discussionmentioning

confidence: 99%

Roles of extracellular nucleotides and P2 receptors in ectodomain shedding

Pupovac

Sluyter

2016

Cell. Mol. Life Sci.

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Ectodomain shedding of integral membrane receptors results in the release of soluble molecules and modification of the transmembrane portions to mediate or modulate extracellular and intracellular signalling. Ectodomain shedding is stimulated by a variety of mechanisms, including the activation of P2 receptors by extracellular nucleotides. This review describes in detail the roles of extracellular nucleotides and P2 receptors in the shedding of various cell surface molecules, including amyloid precursor protein, CD23, CD62L, and members of the epidermal growth factor, immunoglobulin and tumour necrosis factor families. This review discusses the mechanisms involved in P2 receptor-mediated shedding, demonstrating central roles for the P2 receptors, P2X7 and P2Y2, and the sheddases, ADAM10 and ADAM17, in this process in a number of cell types.

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Reduced angiogenesis by marimastat in peritoneal dissemination model of gastric cancer

Cited by 6 publications

References 0 publications

Metabolic Mapping of Proteinase Activity with Emphasis on In Situ Zymography of Gelatinases

Metabolic Mapping of Proteinase Activity with Emphasis on In Situ Zymography of Gelatinases

Runx3 suppresses gastric cancer metastasis through inactivation of MMP9 by upregulation of TIMP‐1

Roles of extracellular nucleotides and P2 receptors in ectodomain shedding

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