Matrix Metalloproteinase Activity in Urine of Patients with Renal Cell Carcinoma Leads to Degradation of Extracellular Matrix proteins: possible use as a Screening Assay

Sherief, Mahmoud H.; Low, Seng Hui; Miura, Masumi; Kudo, Noriko; Novick, Andrew C.; Weimbs, Thomas

doi:10.1097/01.ju.0000049201.91150.9d

Cited by 22 publications

(14 citation statements)

References 16 publications

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“…In these patients, the proteolytic activity of matrix metalloprotease-9 was elevated. 35 In the ES-treated group, the circulating ES levels were 1.52-fold higher than the control group and, corroborating our previous data, 31 these levels caused a reduction of metastatic foci number.…”

Section: Discussionsupporting

confidence: 87%

Endostatin gene therapy stimulates upregulation of ICAM-1 and VCAM-1 in a metastatic renal cell carcinoma model

et al. 2012

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One of the greatest challenges in urological oncology is renal cell carcinoma (RCC), which is the third leading cause of death in genitourinary cancers. RCCs are highly vascularized and respond positively to antiangiogenic therapy. Endostatin (ES) is a fragment of collagen XVIII that possesses antiangiogenic activity. In this study, we examined the potential of ES-based antiangiogenic therapy to activate tumor-associated endothelial cells in metastatic RCC (mRCC). Balb/c-bearing Renca cells were treated with NIH/3T3-LendSN or, as a control, with NIH/3T3-LXSN cells. The T-cell subsets and lymphocyte populations of tumors, mediastinal lymph nodes and the spleen were assessed by flow cytometry. The expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) was assessed by real-time PCR, flow cytometry and immunohistochemistry analysis. ES gene therapy led to an increase in the percentage of infiltrating CD4-interferon (IFN)-g cells (Po0.05), CD8-IFN-g cells (Po0.01) and CD49b-tumor necrosis factor-a cells (Po0.01). In addition, ES therapy caused an increase at the mRNA level of ICAM-1 (1.4-fold; Po0.01) and VCAM-1 (1.5-fold) (control vs treated group; Po0.001). Through flow cytometry, we found a significant increase in the CD34/ICAM-1 cells (8.1-fold; Po0.001) and CD34/VCAM-1 cells (1.6-fold; Po0.05). ES gene therapy induced a significant increase in both T CD4 and CD8 cells in the lymph nodes and the spleen, suggesting that ES therapy may facilitate cell survival or clonal expansion. CD49b cells were also present in increased quantities in all of these organs. In this study, we demonstrate an antitumor inflammatory effect of ES in an mRCC model, and this effect is mediated by an increase in ICAM-1 and VCAM-1 expression in tumor-associated endothelial cells.

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Section: Discussionsupporting

confidence: 87%

Endostatin gene therapy stimulates upregulation of ICAM-1 and VCAM-1 in a metastatic renal cell carcinoma model

et al. 2012

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“…In the urine samples, we found that only few specimens have lytic activity. Our data are in keeping with the data of Cannon and Getzenberg (22) but in contrast with those of Sherief et al (23).…”

Section: Discussioncontrasting

confidence: 51%

Matrix metalloproteinase-2 and -9 in the sera and in the urine of human oncocytoma and renal cell carcinoma

Carlo

2012

Oncology Reports

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Abstract. Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases, capable of degrading all the molecular components of extracellular matrix. MMPs have been shown to play critical roles in tumor cell invasion and metastasis. We verified the activity of MMPs in the sera and in the urine of patients with kidney carcinoma by gelatin zymography. Of these patients, 16 had clear cell renal carcinoma (ccRCC) and 4 patients had oncocytoma. The sera and the urine of 16 healthy subjects were used as controls. In the sera, zymography analysis showed gelatinolytic bands at 72 kDa (gelatinase A) at 92, 130 and 240 kDa (gelatinase B). MMP-9 activity was slightly enhanced in sera from ccRCC compared with oncocytoma patients. Serum MMP-2 activity was similar in ccRCC and in oncocytoma patients. In the urine, 2 oncocytoma patients and 3 (33%) of the ccRCC patients showed gelatinolytic activity, whereas MMPs could not be detected in the concentrated urine of healthy subjects. The most abundant lytic activity was at 92 kDa, whereas MMP-2 was present in lesser quantities. However, there was broad overlap of the data and we did not find any correlation to type, stage or grade. Therefore, despite previous evidence, MMP-2 and -9 activity in serum and urine may not be useful biomarker for kidney carcinomas.

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“…The expression of MMP-9 is increased in malignant tumors in comparison with benign or non-invasive tumors (7,8). In addition, overexpression of MMP-9 is confirmed in renal cell carcinoma (8)(9)(10)(11)(12). Kawada et al reported association of MMP-9 expression and poor prognosis using clinical specimen of renal cell carcinoma (13,14).…”

Section: Introductionmentioning

confidence: 77%

Inhibition of MMP-9 using a pyrrole-imidazole polyamide reduces cell invasion in renal cell carcinoma

Sato¹,

Nagase²,

Obinata³

et al. 2013

International Journal of Oncology

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Abstract.We investigated the clinical significance of the expression levels of matrix metalloproteinase 9 (MMP-9) in renal cell carcinoma (RCC). In addition, we validated the efficacy of pyrrole imidazole polyamide (PIP) targeting MMP-9 on inhibiting proliferation and invasion of RCC. We evaluated the expression levels of MMP-9 in 249 RCC specimens by immunostaining and analyzed the association between MMP-9 expression levels and cancer-specific survival. Furthermore, in a human RCC cell line, Caki-2, we tested the effect of a couple of PIPs targeting MMP-9 one recognizing an NF-κB binding site (MMP-9-NF-κB PIP) and another for the AP-1 binding site (MMP-9-AP-1 PIP) in the MMP-9 promoter. The expression levels of MMP-9, proliferative activity and invasive capability were tested by quantitative PCR, WST8 assay and Matrigel invasion assay, respectively. By immunostaining of the clinical specimens, strong MMP-9 staining was proven to be a significant predictor of poor prognosis for cancer-specific survival (P<0.01). In Caki-2 cells, MMP-9-NF-κB PIP significantly reduced the expression levels of MMP-9 mRNA and inhibited cell invasion, but did not affect the cell proliferation activity. On the other hand, no effect was found in MMP-9-AP-1 PIP on MMP-9 mRNA expression, cell proliferation and invasion. We confirmed the inhibitory effects of MMP-9-NF-κB PIP on the expression of MMP-9 and subsequent invasion of Caki-2 cells. Since it was clearly shown that high MMP-9 expression levels were associated with poor prognosis of RCC, MMP-9 is a potential candidate target for RCC treatment. Transcription therapy using a minor groove binder, such as NF-κB PIP, may be a potential therapeutic agent for RCC, although further investigation is required.

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Matrix Metalloproteinase Activity in Urine of Patients with Renal Cell Carcinoma Leads to Degradation of Extracellular Matrix proteins: possible use as a Screening Assay

Abstract: Analysis of decreased urinary ECM proteins and analysis of increased MMP activity may have value for the development of a sensitive, high throughput molecular screening assay to detect early stage renal cell carcinoma.

Cited by 22 publications

References 16 publications

Endostatin gene therapy stimulates upregulation of ICAM-1 and VCAM-1 in a metastatic renal cell carcinoma model

Endostatin gene therapy stimulates upregulation of ICAM-1 and VCAM-1 in a metastatic renal cell carcinoma model

Matrix metalloproteinase-2 and -9 in the sera and in the urine of human oncocytoma and renal cell carcinoma

Inhibition of MMP-9 using a pyrrole-imidazole polyamide reduces cell invasion in renal cell carcinoma

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