Urinary high molecular weight matrix metalloproteinases as non-invasive biomarker for detection of bladder cancer

Mohammed A Mohammed,Abdel Hady A Abdel Wahab,Mohga S Abdalla,Manar F Seleim,Hayat M Sharada

doi:10.1186/1471-2490-13-25

Mohammed A Mohammed, Abdel Hady A Abdel Wahab + Show 3 more

Open Access

https://doi.org/10.1186/1471-2490-13-25

Copy DOI

Journal: BMC Urology	Publication Date: May 14, 2013
Citations: 39	License type: cc-by

Affiliation: Cairo University, Helwan University

Abstract

BackgroundMatrix Metalloproteinases (MMPs) are key molecules for tumor growth, invasion and metastasis. Over-expression of different MMPs in tumor tissues can disturb the homeostasis and increase the level of various body fluids. Many MMPs including high molecular weights (HMWs) were detected in the urine of prostate and bladder cancer patients. Our aim here is to assess the usefulness of HMW MMPs as non invasive biomarkers in bilharzial bladder cancer in Egyptian patients.MethodsThe activity of different MMPs including HMW species was determined using zymographic analysis technique in the urine samples procured from sixty six bladder cancer patients (bilharzial and non-bilharzial) as well as hundred healthy control subjects. Also, the correlation between these HMW MMPs activities and different clinico-pathological parameters was investigated.ResultsHigh frequency of urine MMPs (uMMPs) activity was determined in 63.6% of examined tumor cases, however, none of the control cases showed any uMMPs activity. MMP-9 had the highest activity (62%) followed by MMP9/NGAL (60%), MMP-2 (54.5%), MMP-9 dimer (53%), ADAMTS (25.6%), and the lowest one was MMP-9/TIMP-1 (12%) only. There was no correlation between uMMPs and any of clinico-pathological parameters including age, gender, tumor size and type, bilharziasis, grade, lymph node involvement, and invasion to the prostate. A significant correlation was established only between MMP-9/TIMP-1 activities with the tumor size.ConclusionsThis study revealed that the detection of urinary MMPs including HMWs activity might be sensitive biomarkers for prediction of bladder cancer. It is also demonstrate that the detection of these urinary HMW gelatinases could not differentiate between bilharzial and non bilharzial bladder cancer subtypes.

Highlights

Matrix Metalloproteinases (MMPs) are key molecules for tumor growth, invasion and metastasis
Enzymatic activity of different MMPs in urine of bladder cancer Matrix Metalloproteinases (MMPs) including high molecular weights were analyzed in urine of bladder cancer patients as well as 100 healthy control subjects using zymographic analysis technique
The highest percent of activity detected was for MMP9 (62%) among all investigated markers followed by MMP9/NGAL (60%), MMP2 (55%), MMP9/dimer (53%), the lowest percent of activity was observed for ADAMTS (25.6%) and MMP9/TIMP-1 (12.1%)

Summary

Introduction

Matrix Metalloproteinases (MMPs) are key molecules for tumor growth, invasion and metastasis. Our aim here is to assess the usefulness of HMW MMPs as non invasive biomarkers in bilharzial bladder cancer in Egyptian patients. Bladder cancer is the most common cancer in Egypt during the past 50 year [1,2]. The most common histopathological type of bladder cancer in Egypt is the squamous cell carcinoma (SCC), constituting from 59% to 81% between 1960–1981 [3]. Oncologists and pathologists have suggested that the ratio between SCC: TCC (transitional cell carcinoma) types of bladder cancer was changed over the past 10–15 years. This is because the change in the etiology of bladder cancer [5]. Non invasive and sensitive method is required for screening, diagnosis or even for monitoring of the disease

Objectives

Methods

Results

Discussion

Conclusion