Tissue inhibitor of metalloproteinases‐1‐induced scattered liver metastasis is mediated by host‐derived urokinase‐type plasminogen activator

Schrötzlmair, Florian; Kopitz, Charlotte; Halbgewachs, Birgit; Lu, Fei; Algül, Hana; Brünner, Nils; Gänsbacher, Bernd; Krüger, Achim

doi:10.1111/j.1582-4934.2009.00951.x

Cited by 19 publications

(21 citation statements)

References 39 publications

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“…It has been confirmed that TIMP-1 is regulated by Bcl-2, which participates in the cellular apoptotic pathway [8]. However, recent reports indicate that TIMP-1 can stimulate cancer development, activate cell growth, promote migration and invasion of cancer cells, and increase the risk of metastasis formation [8][9][10].…”

Section: Introductionmentioning

confidence: 98%

Diagnostic significance of TIMP-1 level in serum and its immunohistochemical expression in colorectal cancer patients

Niewiarowska¹,

Pryczynicz²,

Dymicka-Piekarska³

et al. 2014

pjp

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Tissue inhibitor of metalloproteinase-1 (TIMP-1) inhibits the ability of cancer cells to metastasize, but it can also stimulate cancer development. The aim of this study was to assess the level of TIMP-1 in serum and its expression in patients with colorectal cancer (CRC). The study group consisted of 43 patients diagnosed with colorectal cancer and 24 healthy volunteers. The level of TIMP-1 was assessed by the ELISA method while the expression of this protein was performed immunohistochemically. The concentration of TIMP-1 in the sera of colorectal cancer patients was significantly higher than in the healthy control group (p = 0.004). Higher level of TIMP-1 in the sera correlated with female gender (p = 0.045), tumor location in colon (p = 0.016), poorly differentiated tumor (p = 0.034) and higher platelet count in whole blood (p < 0.004). A positive reaction of the protein in cancer cells was observed in 31 cases and was found to correlate negatively with its reaction in peritumoral stroma (p < 0.001). According to this study, TIMP-1 protein may play an important role in cancer development. The assessment of this molecule in serum and tissue can be useful at the time of diagnosis and can help us to understand the nature of colorectal pathogenesis.

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Section: Introductionmentioning

confidence: 98%

Diagnostic significance of TIMP-1 level in serum and its immunohistochemical expression in colorectal cancer patients

Niewiarowska¹,

Pryczynicz²,

Dymicka-Piekarska³

et al. 2014

pjp

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“…TIMPs might display a dual influence on tumor progression: either beneficial by inhibiting MMPs and impairing angiogenesis or harmful by facilitating cancer cell generation and growth [41,42,43]. Four TIMPs have been characterized in humans (TIMP-1, -2, -3 and -4).…”

Section: Introductionmentioning

confidence: 99%

The Impact of Matrix Metalloproteinases and Their Tissue Inhibitors in Inflammatory Bowel Diseases

Lakatos

Hritz

Varga

et al. 2012

Dig Dis

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Background: It has been suggested that matrix metalloproteinases (MMPs) may play a role in the pathogenesis of inflammatory bowel diseases (IBD). However, the impact of serum MMPs and their inhibitors [tissue inhibitors of metalloproteinases (TIMPs)] have scarcely been investigated in the same experimental setting in ulcerative colitis (UC) and Crohn’s disease (CD) as well as their correlation with IBD activity. Methods: MMP-2, MMP-7, MMP-9, TIMP-1 and TIMP-2 serum antigen levels were determined in 23 patients with UC, 25 patients with CD and 10 healthy control patients by enzyme-linked immunoassay technique. Statistical analysis with one-way ANOVA and Student’s t tests was performed. A linear regression analysis or a Spearman’s r test was used to assess correlation. Differences were considered significant with p < 0.05. Results: Serum antigen concentrations of MMP-9, TIMP-1 and TIMP-2 were significantly higher in UC and CD patients compared to controls. MMP-7 was also significantly higher in CD compared with controls. Elevated MMP-9 and TIMP-1 antigen levels showed significant positive correlation with disease activity of IBD. MMP-2 and TIMP-2 levels inversely correlated with CD activity. Significant correlations were found between MMP-9/TIMP-1 and MMP-2/TIMP-2 antigen levels in both UC and CD. Conclusions: We demonstrated that serum antigen concentrations of MMP-9, TIMP-1 and TIMP-2 were significantly increased in patients with UC and CD compared to controls. Our results suggest that MMPs and TIMPs may contribute to the inflammatory and remodeling processes in IBD. Serum MMP-9 and TIMP-1 might be useful as additional biomarkers in the assessment of IBD activity.

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“…TIMPs might display a dual influence on tumor progression: either beneficial by inhibiting MMPs and impairing angiogenesis, or harmful by facilitating cancer cell generation and growth. TIMPs have strong effects on several biological processes that lead to tumor progression, including those of stimulating cancer cell growth, survival, invasion, angiogenesis and inhibition of apoptosis [57,68,69,70]. …”

Section: The Role Of Proteinasesmentioning

confidence: 99%

The Role of Inflammation and Proteinases in Tumor Progression

Herszényi

Lakatos

Hritz

et al. 2012

Dig Dis

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Chronic inflammation is an important risk factor for the development of cancers. The link between chronic inflammation and the risk of developing cancer is now well established. At least 20% of all cancers arise in association with infection and chronic inflammation. Inflammation and cancer are linked both along intrinsic (driven by genetic events causing malignancy) and extrinsic (driven by inflammatory conditions predisposing to tumor) pathways. Proteinases are key contributors to the breakdown and reconstitution of extracellular matrix components in physiological processes and pathological conditions, including destructive diseases and tumor progression. Matrix metalloproteinases are especially essential in the complex process of coregulation between cellular components of the tumor environment, and they are considered as potential diagnostic and prognostic biomarkers in many types and stages of cancer. Although the link between chronic inflammation, proteinases and risk of developing cancer is now well established, several open questions remain. The most exciting challenge is to find the best approach to target cancer-associated inflammation in patients with cancer. With respect to matrix metalloproteinases, the development of a new generation of selective inhibitors is a promising area of research.

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Tissue inhibitor of metalloproteinases‐1‐induced scattered liver metastasis is mediated by host‐derived urokinase‐type plasminogen activator

Cited by 19 publications

References 39 publications

Diagnostic significance of TIMP-1 level in serum and its immunohistochemical expression in colorectal cancer patients

Diagnostic significance of TIMP-1 level in serum and its immunohistochemical expression in colorectal cancer patients

The Impact of Matrix Metalloproteinases and Their Tissue Inhibitors in Inflammatory Bowel Diseases

The Role of Inflammation and Proteinases in Tumor Progression

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