Up-regulation of gelatinases in the colorectal adenoma-carcinoma sequence

Gimeno–García, Antonio Z.; Rodriguez, Alfredo; Jiménez, Alejandro; Parra‐Blanco, Adolfo; Nicolás–Pérez, David; Paz-Cabrera, Cristina; Dı́az-González, Federico; Medina, Carlos; Díaz‐Flores, Lucio; Quintero, Enrique

doi:10.1016/j.ejca.2006.06.025

Cited by 33 publications

(35 citation statements)

References 30 publications

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“…The gelatinases, specifically MMP 2 and MMP-9, degrade gelatin found in the basement membrane of tissues. The expression of these gelatinases has been reported to be up-regulated in a variety of different cancerous cells [Bachmeier et al, 2001;Gimeno-Garcíaa et al, 2006], and this is a possible reason why these cancers are able to spread throughout the body [Bjö rklund and Koivunen, 2005].Dietary considerations may have an effect/influence on prostate cancer. Certain foods have been associated with a decreased risk of developing cancer, notably fruits and vegetables [Steinmetz and Potter, 1991;Cohen et al, 2000].…”

mentioning

confidence: 97%

Proanthocyanidins from the American Cranberry (Vaccinium macrocarpon) inhibit matrix metalloproteinase‐2 and matrix metalloproteinase‐9 activity in human prostate cancer cells via alterations in multiple cellular signalling pathways

Déziel

Patel

Neto

et al. 2010

J of Cellular Biochemistry

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Prostate cancer is one of the most common cancers in the Western world, and it is believed that an individual's diet affects his risk of developing cancer. There has been an interest in examining phytochemicals, the secondary metabolites of plants, in order to determine their potential anti-cancer activities in vitro and in vivo. In this study we document the effects of proanthocyanidins (PACs) from the American Cranberry (Vaccinium macrocarpon) on matrix metalloproteinase (MMP) activity in DU145 human prostate cancer cells. Cranberry PACs decreased cellular viability of DU145 cells at a concentration of 25 µg/ml by 30% after 6 h of treatment. Treatment of DU145 cells with PACs resulted in an inhibition of both MMPs 2 and 9 activity. PACs increased the expression of TIMP-2, a known inhibitor of MMP activity, and decreased the expression of EMMPRIN, an inducer of MMP expression. PACs decreased the expression of PI-3 kinase and AKT proteins, and increased the phosphorylation of both p38 and ERK1/2. Cranberry PACs also decreased the translocation of the NF-κB p65 protein to the nucleus. Cranberry PACs increased c-jun and decreased c-fos protein levels. These results suggest that cranberry PACs decreases MMP activity through the induction and/or inhibition of specific temporal MMP regulators, and by affecting either the phosphorylation status and/or expression of MAP kinase, PI-3 kinase, NF-κB and AP-1 pathway proteins. This study further demonstrates that cranberry PACs are a strong candidate for further research as novel anti-cancer agents.

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mentioning

confidence: 97%

Proanthocyanidins from the American Cranberry (Vaccinium macrocarpon) inhibit matrix metalloproteinase‐2 and matrix metalloproteinase‐9 activity in human prostate cancer cells via alterations in multiple cellular signalling pathways

Déziel

Patel

Neto

et al. 2010

J of Cellular Biochemistry

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“…MMP-2 and MMP-9 have been studied extensively in colorectal tissues, and their expression is related to basal membrane loss and distant metastasis. In a recent study involving normal colorectal tissue samples, nonadvanced adenomas, advanced adenomas, and cancer samples, MMP-9 activity was markedly enhanced in advanced colorectal neoplasms, showing a progressive upregulation from nonadvanced adenomas to advanced adenomas and CRC [9]. More recently, Hurst et al [10•] assessed the role of MMP-9 as a serum biomarker for CRC detection in 300 symptomatic patients and 46 healthy controls.…”

Section: Matrix Metalloproteinasesmentioning

confidence: 98%

Blood Tests for Early Detection of Colorectal Cancer

Quintero

Gimeno–García

Salido

2009

Curr Colorectal Cancer Rep

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Detection of advanced colorectal neoplasia (advanced adenoma or cancer) in the course of screening programs has been proven to reduce both the incidence and mortality of the disease. In the average-risk population, the most extended colorectal cancer (CRC) screening strategies are based either on annual or biennial fecal occult blood tests, with colonoscopy reserved for patients testing positive, or on endoscopic procedures performed as the primary screening tool every 5 (sigmoidoscopy) or 10 (colonoscopy) years. In addition, other screening procedures, such as CT colonography and fecal DNA analysis, are under current investigation. However, several drawbacks associated with these techniques have led to low acceptability and compliance rates in population-based screenings. Therefore, there is a compelling need to identify noninvasive biomarkers to enhance screening acceptance and efficacy in detecting CRC at an earlier and curable stage. Although the analysis of blood biomarkers has not been included among the recommended strategies for CRC screening yet, recent advances in proteomics and genomics suggest that these technologies may represent alternative or complementary approaches to the currently accepted strategies in the near future. However, the accuracy of these techniques in terms of sensitivity, specificity, and predictive values for early detection of CRC must be confirmed in mass screening studies.

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“…Since MMP9 activity is markedly enhanced in homogenates of advanced adenomas and CRC, 11 we tested the expression of this gelatinase by western blot analysis. 29 Samples were denatured in reducing buffer and loaded (50 g/lane) onto 10% polyacrylamide gels.…”

Section: Metalloproteinase-9 Expressionmentioning

confidence: 99%

“…7---10 Several studies have demonstrated overexpression of these enzymes in tissue samples of CRC compared with colorectal adenomas or normal tissue. 11,12 Other studies have shown increased levels of gelatinases in serum and plasma of patients with CRC compared with healthy controls (HC), and are considered as potential diagnostic biomarkers. 13---16 However, most studies carried out in blood samples have focused on advanced disease 13,15 or on testing the usefulness of gelatinase levels as prognostic biomarkers of recurrence after surgery, 17,18 but not their potential role in the detection of early stages of CRC (advanced adenoma and carcinoma).…”

Section: Introductionmentioning

confidence: 99%