Matrix metalloproteinases (MMPs) in bladder cancer: the induction of MMP9 by epidermal growth factor and its detection in urine

OBJECTIVES To investigate the matrix metalloproteinases (MMPs) 2 and 9 in bladder cancer cell lines stimulated with epidermal growth factor (EGF), and to investigate the presence of gelatinases in the urine of patients with bladder tumours, in relation to the stage and grade of tumour and the EGF re...

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Veröffentlicht in:BJU international 2003-01, Vol.91 (1), p.99-104
Hauptverfasser: Nutt, J.E., Durkan, G.C., Mellon, J.K., Lunec, J.
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creator Nutt, J.E.
Durkan, G.C.
Mellon, J.K.
Lunec, J.
description OBJECTIVES To investigate the matrix metalloproteinases (MMPs) 2 and 9 in bladder cancer cell lines stimulated with epidermal growth factor (EGF), and to investigate the presence of gelatinases in the urine of patients with bladder tumours, in relation to the stage and grade of tumour and the EGF receptor (EGFR) status. PATIENTS, SUBJECTS AND METHODS Conditioned media from cultured tumour cells were analysed by zymography. Urine samples from 28 patients with transitional cell carcinoma and 12 normal volunteers were also analysed. Western blotting was used to verify the bands of gelatinolytic activity. The EGFR status of the tumours was assessed by immunohistochemistry. RESULTS MMP9 was induced by EGF in the RT112 but not the RT4 bladder tumour cell line, whereas MMP2 production was unaffected by EGF. Gelatin zymography of urine samples from patients with bladder tumours showed high levels of MMP activity, with 78% positive for MMP9 and 28% positive for MMP2. The total gelatinolytic and MMP9 activity were significantly higher in patients with high‐stage invasive tumours than in those with superficial tumours (P 
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PATIENTS, SUBJECTS AND METHODS Conditioned media from cultured tumour cells were analysed by zymography. Urine samples from 28 patients with transitional cell carcinoma and 12 normal volunteers were also analysed. Western blotting was used to verify the bands of gelatinolytic activity. The EGFR status of the tumours was assessed by immunohistochemistry. RESULTS MMP9 was induced by EGF in the RT112 but not the RT4 bladder tumour cell line, whereas MMP2 production was unaffected by EGF. Gelatin zymography of urine samples from patients with bladder tumours showed high levels of MMP activity, with 78% positive for MMP9 and 28% positive for MMP2. The total gelatinolytic and MMP9 activity were significantly higher in patients with high‐stage invasive tumours than in those with superficial tumours (P &lt; 0.05), and were higher than in normal controls. Gelatinolytic activity at 130 and 200 kDa in urine was identified as MMP9 and MMP2. There was no significant relationship of urinary MMP9 activity to EGFR status of the tumour. CONCLUSION EGF induces MMP9 but not MMP2 in bladder cells. Analysis of urinary gelatinases is a useful noninvasive technique and both total gelatinase and MMP9 activity are associated with high stages of bladder tumours.</description><identifier>ISSN: 1464-4096</identifier><identifier>EISSN: 1464-410X</identifier><identifier>DOI: 10.1046/j.1464-410X.2003.04020.x</identifier><identifier>PMID: 12614260</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>Biological and medical sciences ; bladder cancer ; Blotting, Western ; epidermal growth factor ; Epidermal Growth Factor - physiology ; human bladder cell lines ; Humans ; Matrix Metalloproteinase 2 - metabolism ; Matrix Metalloproteinase 2 - urine ; Matrix Metalloproteinase 9 - metabolism ; Matrix Metalloproteinase 9 - urine ; matrix metalloproteinases (MMP) ; Matrix Metalloproteinases - metabolism ; Medical sciences ; Neoplasm Proteins - metabolism ; Nephrology. Urinary tract diseases ; Tumor Cells, Cultured ; Tumors of the urinary system ; Urinary Bladder Neoplasms - enzymology ; Urinary Bladder Neoplasms - urine ; Urinary tract. 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PATIENTS, SUBJECTS AND METHODS Conditioned media from cultured tumour cells were analysed by zymography. Urine samples from 28 patients with transitional cell carcinoma and 12 normal volunteers were also analysed. Western blotting was used to verify the bands of gelatinolytic activity. The EGFR status of the tumours was assessed by immunohistochemistry. RESULTS MMP9 was induced by EGF in the RT112 but not the RT4 bladder tumour cell line, whereas MMP2 production was unaffected by EGF. Gelatin zymography of urine samples from patients with bladder tumours showed high levels of MMP activity, with 78% positive for MMP9 and 28% positive for MMP2. The total gelatinolytic and MMP9 activity were significantly higher in patients with high‐stage invasive tumours than in those with superficial tumours (P &lt; 0.05), and were higher than in normal controls. Gelatinolytic activity at 130 and 200 kDa in urine was identified as MMP9 and MMP2. There was no significant relationship of urinary MMP9 activity to EGFR status of the tumour. CONCLUSION EGF induces MMP9 but not MMP2 in bladder cells. Analysis of urinary gelatinases is a useful noninvasive technique and both total gelatinase and MMP9 activity are associated with high stages of bladder tumours.</description><subject>Biological and medical sciences</subject><subject>bladder cancer</subject><subject>Blotting, Western</subject><subject>epidermal growth factor</subject><subject>Epidermal Growth Factor - physiology</subject><subject>human bladder cell lines</subject><subject>Humans</subject><subject>Matrix Metalloproteinase 2 - metabolism</subject><subject>Matrix Metalloproteinase 2 - urine</subject><subject>Matrix Metalloproteinase 9 - metabolism</subject><subject>Matrix Metalloproteinase 9 - urine</subject><subject>matrix metalloproteinases (MMP)</subject><subject>Matrix Metalloproteinases - metabolism</subject><subject>Medical sciences</subject><subject>Neoplasm Proteins - metabolism</subject><subject>Nephrology. Urinary tract diseases</subject><subject>Tumor Cells, Cultured</subject><subject>Tumors of the urinary system</subject><subject>Urinary Bladder Neoplasms - enzymology</subject><subject>Urinary Bladder Neoplasms - urine</subject><subject>Urinary tract. 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Urinary tract diseases</topic><topic>Tumor Cells, Cultured</topic><topic>Tumors of the urinary system</topic><topic>Urinary Bladder Neoplasms - enzymology</topic><topic>Urinary Bladder Neoplasms - urine</topic><topic>Urinary tract. Prostate gland</topic><topic>urine</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Nutt, J.E.</creatorcontrib><creatorcontrib>Durkan, G.C.</creatorcontrib><creatorcontrib>Mellon, J.K.</creatorcontrib><creatorcontrib>Lunec, J.</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>BJU international</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Nutt, J.E.</au><au>Durkan, G.C.</au><au>Mellon, J.K.</au><au>Lunec, J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Matrix metalloproteinases (MMPs) in bladder cancer: the induction of MMP9 by epidermal growth factor and its detection in urine</atitle><jtitle>BJU international</jtitle><addtitle>BJU Int</addtitle><date>2003-01</date><risdate>2003</risdate><volume>91</volume><issue>1</issue><spage>99</spage><epage>104</epage><pages>99-104</pages><issn>1464-4096</issn><eissn>1464-410X</eissn><abstract>OBJECTIVES To investigate the matrix metalloproteinases (MMPs) 2 and 9 in bladder cancer cell lines stimulated with epidermal growth factor (EGF), and to investigate the presence of gelatinases in the urine of patients with bladder tumours, in relation to the stage and grade of tumour and the EGF receptor (EGFR) status. PATIENTS, SUBJECTS AND METHODS Conditioned media from cultured tumour cells were analysed by zymography. Urine samples from 28 patients with transitional cell carcinoma and 12 normal volunteers were also analysed. Western blotting was used to verify the bands of gelatinolytic activity. The EGFR status of the tumours was assessed by immunohistochemistry. RESULTS MMP9 was induced by EGF in the RT112 but not the RT4 bladder tumour cell line, whereas MMP2 production was unaffected by EGF. Gelatin zymography of urine samples from patients with bladder tumours showed high levels of MMP activity, with 78% positive for MMP9 and 28% positive for MMP2. The total gelatinolytic and MMP9 activity were significantly higher in patients with high‐stage invasive tumours than in those with superficial tumours (P &lt; 0.05), and were higher than in normal controls. Gelatinolytic activity at 130 and 200 kDa in urine was identified as MMP9 and MMP2. There was no significant relationship of urinary MMP9 activity to EGFR status of the tumour. CONCLUSION EGF induces MMP9 but not MMP2 in bladder cells. Analysis of urinary gelatinases is a useful noninvasive technique and both total gelatinase and MMP9 activity are associated with high stages of bladder tumours.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>12614260</pmid><doi>10.1046/j.1464-410X.2003.04020.x</doi><tpages>6</tpages></addata></record>
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source Wiley Online Library - AutoHoldings Journals; MEDLINE
subjects Biological and medical sciences
bladder cancer
Blotting, Western
epidermal growth factor
Epidermal Growth Factor - physiology
human bladder cell lines
Humans
Matrix Metalloproteinase 2 - metabolism
Matrix Metalloproteinase 2 - urine
Matrix Metalloproteinase 9 - metabolism
Matrix Metalloproteinase 9 - urine
matrix metalloproteinases (MMP)
Matrix Metalloproteinases - metabolism
Medical sciences
Neoplasm Proteins - metabolism
Nephrology. Urinary tract diseases
Tumor Cells, Cultured
Tumors of the urinary system
Urinary Bladder Neoplasms - enzymology
Urinary Bladder Neoplasms - urine
Urinary tract. Prostate gland
urine
title Matrix metalloproteinases (MMPs) in bladder cancer: the induction of MMP9 by epidermal growth factor and its detection in urine
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