The role of urinary proteases in bladder cancer

Abstract

Bladder cancer (BCa) is one of the most prevalent malignancies worldwide. Riskfactors for BCa are well established and include smoking and infections, whichcan lead to immune system activation, altered gene expression patterns, proteolytic activity, tissue damage, and, ultimately, cancer development. Urinehas become one of the most attractive diagnosis samples, and, notably, urineprofiling by mass spectrometry allows the simultaneously analysis of multipleenzymes and their interactors, substrates, inhibitors, and regulators, providing anintegrative view of enzymatic dynamics. Most BCa-associated enzymaticalterations take place at the level of proteases, being MMP-9, MMP-2, urokinase-type plasminogen activator, cathepsin D, and cathepsin G alreadyrelated to BCa development and progression. Herein, we overview the role of proteases and the classes more studied in BCa pathogenesis, as well as themethodologies used for assessing protease amount and activity in urine samples, highlighting its advantages and limitations, and the value of urinary proteases asdisease biomarkers.