Imbalance between Matrix Metalloproteinase 9 and Tissue Inhibitor of Metalloproteinases 1 Expression by Tumor Cells Implicated in Liver Metastasis from Colorectal Carcinoma.

Osuga, Yutaka; Miura, Kazuhide; Ohkita, Akira; Nagase, Hideaki; Shirouzu, Kazuo

doi:10.2739/kurumemedj.48.211

Cited by 20 publications

(14 citation statements)

References 15 publications

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“…Their natural tissue inhibitors (TIMPs) are induced in stromal cells to regulate the proteinase reactions [27]. Increased expression of MMPs and TIMPs plays a key role in CRC invasion and/or metastasis [28]. It was observed that the levels of MMP-9 and TIMP-1 were elevated in CRC patients in relation to healthy controls [7, 16–18].…”

Section: Discussionmentioning

confidence: 99%

The diagnostic value of matrix metalloproteinase 9 (MMP-9) and tissue inhibitor of matrix metalloproteinases 1 (TIMP-1) determination in the sera of colorectal adenoma and cancer patients

Mroczko

Groblewska

Okulczyk

et al. 2010

Int J Colorectal Dis

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PurposeTumor cells, including colorectal cancer (CRC), are able to produce and release matrix metalloproteinase 9 (MMP-9) which is involved in tumor invasion and metastasis. Natural tissue inhibitors of matrix metalloproteinases (TIMPs) regulate activity of MMPs and stimulate tumor growth and malignant transformation. The aim of the present study was to compare the clinical significance of serum MMP-9 with TIMP-1 in the diagnosis of CRC patients and in the differentiation between colorectal adenoma (CA) and cancer.MethodsSerum MMP-9 and TIMP-1 were measured in 75 CRC patients, 35 CA, and 70 healthy subjects using enzyme-linked immunosorbent assay. Concentrations of carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA 19-9) were determined by microparticle enzyme immunoassay.ResultsSerum levels of all proteins tested were significantly higher in CRC patients than in healthy subjects. Additionally, serum TIMP-1 was significantly higher in patients with CRC than in CA patients. Concentrations of TIMP-1 correlated with tumor stage, nodal involvement, presence of distant metastases, patients' survival, and tumor resectability. Diagnostic sensitivity of TIMP-1 was higher (61%) than those of other biomarkers (MMP-9, 55%; CEA, 39%; CA 19-9, 11%), and increased in combined use with MMP-9 (75%) or CEA (73%). The areas under receiver operating characteristic curves of TIMP-1 were larger than those of MMP-9.ConclusionsOur findings suggest better usefulness of serum TIMP-1 than MMP-9 in the diagnosis of CRC, especially in the assessment of Duke's classification of tumor stage, survival of cancer patients, resectability of tumor, and in the differentiation between CA and cancer.

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Section: Discussionmentioning

confidence: 99%

The diagnostic value of matrix metalloproteinase 9 (MMP-9) and tissue inhibitor of matrix metalloproteinases 1 (TIMP-1) determination in the sera of colorectal adenoma and cancer patients

Mroczko

Groblewska

Okulczyk

et al. 2010

Int J Colorectal Dis

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“…In cancer tissue, however, it is suspected that this balance is disrupted, that MMPs become predominant, and that invasion and metastasis of cancer cells proceeds (13,14). Ogata et al reported that, in experimental and clinical colorectal cancer, the expression of MMP-9 mRNA and TIMP-1 mRNA in tumor cells correlated with liver metastasis, but that there was no relation between the expression of these in stromal cells and liver metastasis (32). These findings suggested that the expression of MMP-9 mRNA and TIMP-1 mRNA in tumor cells is more closely related to the biological behavior of the tumor than is their expression in stromal cells.…”

Section: Discussionmentioning

confidence: 99%

Etodolac, a selective cyclooxygenase-2 inhibitor, inhibits liver metastasis of colorectal cancer cells via the suppression of MMP-9 activity

Ishizaki

Katsumata²,

Tsuchida³

et al. 2006

Int J Mol Med

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Abstract. Synchronous or metachronous liver metastasis occurs in approximately 15% of colorectal cancer patients and is an important negative prognostic factor. We therefore need an effective therapy to prevent metastasis. It has become apparent that cyclooxygenase (COX)-2 plays an important role in cancer growth, invasion and metastasis and that there is potential for chemoprevention via inhibition of these processes. We injected colon 26, a colorectal cancer cell line, in CDF1 mouse spleen and, from the following day, two kinds of COX-2 inhibitor (etodolac and nimesulide) were administered orally. Two weeks later, the animals were sacrificed, the liver was excised, and we counted the number of metastatic nodules on the liver surface. In addition, COX-2 mRNA, matrix metalloproteinase (MMP)-9 mRNA, and tissue inhibitor of MMP (TIMP)-1 mRNA of cancer tissue were measured by means of real-time RT-PCR. The number of metastatic nodules on the liver surface was significantly lower in the etodolac-treated group than in controls (p=0.001), but no significant difference was noted in the nimesulide-treated group. The expression of COX-2 mRNA was also significantly lower in the etodolactreated group than in controls (p=0.04), but not in the nimesulide-treated group. In addition, the expression of MMP-9 mRNA was significantly lower in the etodolac group than in controls (p=0.02), but not in the nimesulide group. Among the groups, there were no significant differences in TIMP-1 mRNA. Expression of COX-2 mRNA and MMP-9 mRNA correlated significantly (r=0.78, p=0.001), but there was no correlation between either COX-2 mRNA and TIMP-1 mRNA expression or between MMP-9 mRNA and TIMP-1 mRNA expression. These findings indicate that the selective COX-2 inhibitor, etodolac, suppresses liver metastasis by reducing MMP-9 activity.

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“…The second is cleavage of the propeptides by other MMPs (N a g a s e et al, 1991; A i m e s , Q u i g l e y , 1995; Anand- Apte et al, 1996;Ogata et al, 2001).…”

Section: Matrix Metalloproteinasementioning

confidence: 99%

Zinc in the Animal Organism: A Review

Sloup

Jankovská

Nechybová

et al. 2017

Scientia Agriculturae Bohemica

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Zinc, as an essential metal, is necessary for the correct function of an organism. It is involved in biochemical processes that affect the immune response of an organism, and it acts as a neuromodulator in the excitatory synapses of the brain. Zinc is also applied in response to stressful stimuli. Zinc is an essential factor of gene expression and is important, at the cellular level, in maintaining the integrity of the cell walls. It influences organism ageing. Zinc is relatively abundant in nature, and it exists in a mineral form and rarely as a pure element. Zinc is used widely in industry and agriculture. In industry, it is utilized mainly in the processing of other metals as protection against corrosion. In agriculture, it is used in fertilizers and chemicals to produce pesticides. In certain areas affected by human activities, its concentrations increase, and large quantities of this metal can get into the food supply. In this paper, we focus on zinc metabolism and homeostasis, with an emphasis placed on the biological function of zinc. This study also deals with zinc deficiency and its effect on health. We also touch on the excessive intake of zinc and its toxicity. metal, enzyme, protein, metallothionein

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Imbalance between Matrix Metalloproteinase 9 and Tissue Inhibitor of Metalloproteinases 1 Expression by Tumor Cells Implicated in Liver Metastasis from Colorectal Carcinoma.

Cited by 20 publications

References 15 publications

The diagnostic value of matrix metalloproteinase 9 (MMP-9) and tissue inhibitor of matrix metalloproteinases 1 (TIMP-1) determination in the sera of colorectal adenoma and cancer patients

The diagnostic value of matrix metalloproteinase 9 (MMP-9) and tissue inhibitor of matrix metalloproteinases 1 (TIMP-1) determination in the sera of colorectal adenoma and cancer patients

Etodolac, a selective cyclooxygenase-2 inhibitor, inhibits liver metastasis of colorectal cancer cells via the suppression of MMP-9 activity

Zinc in the Animal Organism: A Review

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