AUTHOR=Synelnyk Tatyana , Vovk Tetiana , Halenova Tetiana , Tytarenko Valentyn , Raksha Nataliia , Savchuk Olexii , Falalyeyeva Tetyana , Ostapchenko Liudmyla , Yakovlev Pavel , Kozyk Marko , Thorley Dominic , Strubchevska Kateryna 

TITLE=Evaluation of proteolytic activity and serine proteases distribution in plasma from patients with bladder cancer

JOURNAL=Frontiers in Medicine

VOLUME=Volume 10 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2023.1276882

DOI=10.3389/fmed.2023.1276882

ISSN=2296-858X

ABSTRACT=Bladder cancer (BC) is an aggressive disease with a poor prognosis. A bladder tumor, like other malignant neoplasms, is characterized by the presence of both cancer cells and stromal cells which secrete cytokines, chemokines, growth factors, and proteolytic enzymes. One such class of proteolytic enzymes are serine proteases, which take part in the tumor microenvironment formation via supporting and contributing to tumor progression. This study aims to evaluate the proteolytic activity and serine protease contribution in plasma from BC patients.Methods: The research involved patients of Alexandrovsky city clinical hospital aged 52 -76 with transitional cell carcinoma of the bladder. Plasma plasminogen levels were determined by enzyme-linked immunosorbent assay, and the potential activity was measured by chromogenic plasminogen assay. Serine proteases fractions were obtained by the affinity chromatography method, and enzyme concentration in the selected fractions were determined by the Bradford method. Serine proteases distribution was investigated by electrophoresis in a polyacrylamide gel. It was determined that the concentration, potential activity of plasminogen, and the total amount of serine proteases in plasma from BC patients were greater than the values of the corresponding indicators in healthy donors. This could be one of the factors contributing to increased proteolysis seen in the process of carcinogenesis. Plasminogen concentration in BC patients with stage IV disease; however, displayed a tendency to be reduced compared to earlier stages, and the potential activity of plasminogen was significantly lower in patients with stages III -IV BC. A  tumor stage specific gradual decline in the serine protease plasma content was shown. The results of electrophoretic analysis established a significant diminishment in the percentage of high molecular weight components (under non-reducing conditions) and their complete disappearance in plasma serine protease fractions from BC patients. A decline in the percentage of heavy and light plasmin chains in BC patients was also observed.The results indicate significant changes in the proteolytic activity of plasma, from BC patients when compared to healthy controls, which is accompanied by alterations in serine protease distribution caused by tumor microenvironment pecularlities at the different stages of oncopathology.