Noninvasive Diagnosis of Bladder Cancer by Detection of Matrix Metalloproteinases (MMP-2 and MMP-9) and Their Inhibitor (TIMP-2) in Urine

Eissa, Sanaa; Ali-Labib, Randa; Swellam, Menha; Bassiony, Manal; Tash, Fathy; Elzayat, Tarek

doi:10.1016/j.eururo.2007.04.006

Cited by 95 publications

(58 citation statements)

References 23 publications

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“…Within the MMP family, MMP2 (gelatinase A, 72 kDa) cleaves type IV collagen and gelatin, which are the main structural components of the basal membrane (3). Expression of MMP2 has been implicated in the development and progression of many neoplasias, such as bladder (4) and colon cancer (5).…”

Section: Introductionmentioning

confidence: 99%

Underexpression of MMP-2 and its regulators, TIMP2, MT1-MMP and IL-8, is associated with prostate cancer

et al. 2012

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Prostate cancer (PCa) is a common disease with a multifactorial and complex etiology. It is the most common malignancy in the male and the second leading cause of death in many countries, including Brazil. Estimates for 2011 indicate that 903,500 new cases and 258,400 deaths relatVol. 38 (2): 167-174; March -April, 2012 Objective: Extracellular matrix homeostasis is strictly maintained by a coordinated balance between the expression of metalloproteinases (MMPs) and their regulators. The purpose of this study was to investigate whether MMP-2 and its specifi c regulators, TIMP-2, MT1-MMP and IL-8, are expressed in a reproducible, specifi c pattern and if the profi les are related to prognosis and clinical outcome of prostate cancer (PCa). Materials and Methods: MMP-2, TIMP-2, MT1-MMP and IL-8 expression levels were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) in freshly frozen malignant and benign tissue specimens collected from 79 patients with clinically localized PCa who underwent radical prostatectomies. The control group consisted of 11 patients with benign prostate hyperplasia (BPH). The expression profi le of the MMP-2 and its regulators were compared using Gleason scores, pathological stage, pre-operative PSA levels and the fi nal outcome of the PCa. Results: The analysis of 79 specimens of PCa revealed that MMP-2, TIMP-2, MT1-MMP and IL-8 were underexpressed at 60.0%, 72.2%, 62.0% and 65.8%, respectively, in malignant prostatic tissue in relation to BPH samples. Considering the prognostic parameters, we demonstrated that high Gleason score tumors (≥ 7) overexpressed MMP-2 (p = 0.048) and TIMP-2 (p = 0.021), compared to low Gleason score tumors (< 7). Conclusion: We have demonstrated that MMP-2 and its regulators are underexpressed in PCa. Alternatively, overexpression of MMP-2 and TIMP-2 was related to higher Gleason score tumors. We postulate that alterations in metalloproteinase expression may be important in the control of tissue homeostasis related to prostate carcinogenesis and tumor behavior. Underexpression of MMP-2 and its

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Section: Introductionmentioning

confidence: 99%

Underexpression of MMP-2 and its regulators, TIMP2, MT1-MMP and IL-8, is associated with prostate cancer

et al. 2012

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“…Additional studies were excluded as they were not case-control or cohort studies (n=19), were irrelevant to the present study (n=4) or possessed incomplete data (n=1). Overall, 23 case-control studies (15,(18)(19)(20)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47), published between 1998 and 2014, were selected for meta-analysis, and consisted of 1,040 bladder cancer patients and 244 healthy control individuals. Among the 23 studies, the study subjects in 3 studies were African, 14 studies enrolled Asian subjects and 6 studies enrolled Caucasian subjects.…”

Section: Resultsmentioning

confidence: 99%

Elevated matrix metalloproteinase-9 expression may contribute to the pathogenesis of bladder cancer

Zeng

Cen²,

Kang³

2016

Oncology Letters

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Abstract. The present study investigated the potential association between matrix metalloproteinase-9 (MMP-9) expression and the pathogenesis of bladder cancer. The present study reviewed previous studies published in Chinese and English using predefined selection criteria, which identified high-quality studies concerning MMP-9 and bladder cancer. Statistical analyses of the data were conducted using Comprehensive Meta-Analysis software version 2.0. In total, 23 case-control studies were selected, which consisted of 1,040 bladder cancer patients and 244 healthy controls. The expression rates and protein levels of MMP-9 were significantly increased in bladder cancer patients compared with the healthy controls, which was demonstrated using immunohistochemistry (IHC) and enzyme-linked immunosorbent assay-based methods. Furthermore, the expression rate of MMP-9 in histological G1/G2 grade bladder cancer tumors was significantly decreased compared with G3 tumors. Subgroup analysis based on ethnicity demonstrated that the rate of MMP-9 protein expression between bladder cancer patients and healthy controls was significantly different in African, Asian and Caucasian patients, which was identified using IHC. The MMP-9 protein levels in bladder cancer patients and healthy controls were significantly different between Asian and Caucasian patients, but not African patients. The differences between MMP-9 expression in ethnic groups were also evident in the expression rate of MMP-9 identified in histological G1/G2 grade tumors in Asian and Caucasian patients compared with G3 grade tumors, which was not evident in African patients. In conclusion, the present meta-analysis results markedly indicate that MMP-9 expression is associated with clinicopathological features of bladder cancer, suggesting that MMP-9 may be a useful biomarker in the diagnosis and clinical management of bladder cancer, and may be a valuable therapeutic target. IntroductionWorldwide, bladder cancer is the 7th most common cancer in men and the 17th most common cancer in women (1). Notably, in the developed world, bladder cancer ranks as the 4th and 9th most common cancer in men and women, respectively (2). An estimated 375,000 bladder cancer cases are reported each year around the world, with 68,810 novel cases and ~14,100 mortalities reported in the United States in 2013 (3). Transitional cell carcinoma is the most frequently occurring type of bladder cancer. Other bladder cancer types consist of adenocarcinoma, squamous cell carcinoma and small cell bladder cancer (4,5). Notably, the incidence of bladder cancer increases with age, particularly in men (6). Bladder cancer arises as a result of multistep alterations, among which metastasis is crucial (7). Epidemiological studies have demonstrated that several environmental factors may contribute to bladder cancer risk, including smoking, chronic inflammation, radiation exposure, anticancer drugs and aromatic amines, which are contained in dyes (6,8). The treatment of bladder cancer is based on multiple para...

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“…MMPs, of which several isoforms are known, have a major role in matrix destruction and are involved in metastasis by mediating basement membrane destruction and angiogenesis (Kim et al, 2004). Of all known isoforms, MMP-2 and MMP-9 are strongly associated with invasion in bladder cancer (Eissa et al, 2007;Papathoma et al, 2000). Cathepsins have also been involved in cancer invasion.…”

Section: Proteolytic Enzymes In Bladder Cancer Invasionmentioning

confidence: 99%

Animal Models for Basic and Preclinical Research in Bladder Cancer

Eiján¹,

Lodillinsky²,

Sandes³

2012

Bladder Cancer - From Basic Science to Robotic Surgery

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Noninvasive Diagnosis of Bladder Cancer by Detection of Matrix Metalloproteinases (MMP-2 and MMP-9) and Their Inhibitor (TIMP-2) in Urine

Cited by 95 publications

References 23 publications

Underexpression of MMP-2 and its regulators, TIMP2, MT1-MMP and IL-8, is associated with prostate cancer

Underexpression of MMP-2 and its regulators, TIMP2, MT1-MMP and IL-8, is associated with prostate cancer

Elevated matrix metalloproteinase-9 expression may contribute to the pathogenesis of bladder cancer

Animal Models for Basic and Preclinical Research in Bladder Cancer

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