Matrix metalloproteinase 2 and 9 activity in patients with colorectal cancer liver metastasis

Waas, Erwin T.; Wobbes, Theo; Lomme, Roger M. L. M.; DeGroot, Jeroen; Ruers, Theo J.M.; Hendriks, T.

doi:10.1002/bjs.4346

Cited by 71 publications

(49 citation statements)

References 17 publications

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“…Furthermore, the upregulation of these MMPS has been associated with the poor prognosis of patients with bladder cancer (19)(20)(21). Therefore, the inhibition of MMP expression may be considered an early target for the prevention of cancer metastasis (22,23). The present study demonstrated that resveratrol decreased the secretion of MMP-2 and MMP-9 protein in a dose-dependent manner in T24 cells.…”

Section: Discussionsupporting

confidence: 54%

Inhibitory effects of resveratrol on the adhesion, migration and invasion of human bladder cancer cells

Bai

Yang

Zhang

et al. 2016

Molecular Medicine Reports

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Abstract.Resveratrol is a polyphenolic compound, which has been revealed to induce apoptosis in numerous human cancer cells; however, the effects of resveratrol on the migration and invasion of human bladder cancer cells have not been reported. The present study aimed to evaluate the anti-metastatic potential of resveratrol against bladder cancer and its mechanism of action. The results indicated that resveratrol inhibits the adhesion, migration and invasion of bladder cancer cells in a dose-dependent manner. Resveratrol was shown to significantly inhibit the expression and secretion of matrix metalloproteinase (MMP)-2 and MMP-9 in bladder cancer cells. Furthermore, resveratrol suppressed the phosphorylation of c-Jun N-terminal kinase and extracellular signal-regulated protein kinase. In conclusion, the present study is the first, to the best of our knowledge, to demonstrate that resveratrol may be considered a novel anticancer agent for the treatment of bladder cancer via the inhibition of migration and invasion. IntroductionBladder cancer is the fourth most common type of cancer, and was the cause of >11,510 cases of cancer-associated mortality among men in the USA in 2014 (1). The majority of bladder cancer cases are noninvasive, low-grade transitional cell carcinoma (TCC); however, ≤30% of all diagnosed tumors are classified as invasive TCC, which is associated with high mortality (2). Notably, among all of the various types of cancer, bladder cancer exhibits a significantly high incidence of recurrence post-treatment, and therefore is recognized as the most expensive cancer to treat. Due to the high prevalence and frequent tumor recurrence associated with bladder cancer, the exploration of preventative strategies is required.Previous epidemiological and scientific studies have indicated that plant-derived phytochemicals may be beneficial in the prevention and treatment of cancer (3-5). Resveratrol is a polyphenolic compound, which is present in grapes (red wine), knotweed, peanuts, mulberries and other plants. Numerous studies have suggested that resveratrol may prevent the progression of various pathologies, including vascular diseases, ischemic injuries, cancer and neurodegenerative disorders (6-8). Furthermore, it has previously been confirmed that resveratrol exerts antiproliferative and/or apoptotic effects on leukemia, prostate, breast and colon cancers cells in vitro (9-12). Previous studies regarding the anticancer effects of resveratrol have focused on its anti-invasive and anti-metastatic activities (13-15). However, to the best of our knowledge, there is currently no evidence as to whether resveratrol may inhibit the migration and invasion of human bladder cancer cells.Metastasis is one of the hallmarks of advanced cancer progression, and cancer cell migration and invasion are crucial events in bladder cancer metastasis. Matrix metalloproteinases (MMPs), including MMP-2 and MMP-9, degrade the basement membrane and extracellular matrix (ECM), and are therefore considered crucial proteolytic protei...

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Section: Discussionsupporting

confidence: 54%

Inhibitory effects of resveratrol on the adhesion, migration and invasion of human bladder cancer cells

Bai

Yang

Zhang

et al. 2016

Molecular Medicine Reports

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“…It was suggested that the enhanced cell surface expression of MMPs and TIMPs on inflammatory cells in cancer tissue might be a result of a host response induced by tumors [19]. Increased expression of MMP-2 might play a key role in colorectal cancer invasion and/or metastasis [20,21]. Moreover, it was shown that in colon and rectal tumor tissues MMP-2 protein levels were higher, while TIMP-2 significantly lower than in corresponding paired normal mucosa [22].…”

Section: Discussionmentioning

confidence: 99%

Matrix metalloproteinase 2 and tissue inhibitor of matrix metalloproteinases 2 in the diagnosis of colorectal adenoma and cancer patients.

Groblewska¹,

Mroczko²,

Gryko³

et al. 2011

Folia Histochem Cytobiol.

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Abstract:The aim of the study was to assess the importance of the measurement of matrix metalloproteinase 2 (MMP-2) and tissue inhibitor of matrix metalloproteinases 2 (TIMP-2) in patients with colorectal cancer (CRC) in relation to clinicopathological features of tumor and patients' survival. Additionally, we determined serum MMP-2 and TIMP-2 in colorectal adenoma (CA) patients and healthy controls and compared them with tumor markers, CEA and CA 19-9. The serum levels of MMP-2 and TIMP-2 in 91 CRC patients, 28 CA subjects and 91 healthy controls were determined by ELISA method, but concentrations of CEA and CA 19-9 using MEIA method. Nonparametric statistical analyses were used. Serum levels of MMP-2 and TIMP-2 were significantly lower in CRC patients than in healthy subjects and decreased with tumor stage. Additionally, MMP-2 concentrations were significantly lower in patients with CRC than in CA group. Diagnostic sensitivity of TIMP-2 (59%) was the highest among biomarkers tested and increased in combined use with CEA (79%). Moreover, the area under ROC curve (AUC) of TIMP-2 was larger than AUC of MMP-2 in differentiation between CRC and healthy subjects, but lower than AUC of matrix metalloproteinase 2 in differentiation between colorectal cancer and adenoma. Our findings suggest clinical usefulness of TIMP-2 as a biomarker in the diagnosis of CRC, especially in combination with CEA. However, further investigation is necessary.

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“…Although its role in metastatic tumor cell growth is still unclear, increased MMP expression is frequently accompanied by tumor metastasis and suppression of MMP expression could be used as a growth inhibitory treatment to prevent tumor metastasis. 23,27,28 When pshHIF-1a was administered to tumor-bearing mice by the hydrodynamics-based procedure, a significant reduction in the number of tumor cells was observed (Figure 6a). This result indicates that HIF-1a expression in either tumor cells or hepatic normal cells or in both types of cells plays an important role in tumor progression.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of tumor cell growth in the liver by RNA interference-mediated suppression of HIF-1α expression in tumor cells and hepatocytes

2008

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Hypoxia-inducible factor-1 (HIF-1) is a ubiquitously expressed oxygen-regulated transcription factor composed of a and b subunits. HIF-1 activates transcription of various genes including those involved in metastatic tumor growth. In the present study, HIF-1a expression in tumor-bearing mouse liver was examined after inoculation of tumor cells into portal vein. We found that tumor-bearing liver showed greatly increased HIF-1a expression. Plasmid DNA (pDNA) expressing short hairpin RNA targeting HIF-1a (pshHIF-1a) was effective in suppressing protein expression of HIF-1a in vitro. Intravenous injection of pshHIF-1a by hydrodynamics-based procedure reduced the HIF-1a protein expression in both normal and tumor cells and tumor cell number in the liver. Pre-injection of pshHIF-1a to mice, by which pDNA was delivered only to liver cells, not to tumor cells, was also effective in reducing the number of tumor cells inoculated 3 days after pDNA injection. These findings indicate that HIF-1a expression is increased in normal liver cells as well as tumor cells, and HIF-1a expression plays an important role in tumor progression. Use of the RNA interference (RNAi) of HIF-1 is an effective strategy for inhibiting tumor cell growth, and both tumor and normal cells can be the target for RNAi-based anticancer treatment.

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Matrix metalloproteinase 2 and 9 activity in patients with colorectal cancer liver metastasis

Abstract: These data suggest a role for MMPs in colorectal cancer liver metastasis, but indicate different roles for individual MMPs.

Cited by 71 publications

References 17 publications

Inhibitory effects of resveratrol on the adhesion, migration and invasion of human bladder cancer cells

Inhibitory effects of resveratrol on the adhesion, migration and invasion of human bladder cancer cells

Matrix metalloproteinase 2 and tissue inhibitor of matrix metalloproteinases 2 in the diagnosis of colorectal adenoma and cancer patients.

Inhibition of tumor cell growth in the liver by RNA interference-mediated suppression of HIF-1α expression in tumor cells and hepatocytes

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