Proteolytic activity in chronic pancreatitis and pancreatic cancer

BACKGROUND: The aim of this study was to address the diagnostic challenges associated with pancreatic disorders, such as chronic pancreatitis (CP) and pancreatic cancer (PC) and highlight the importance of protease activity as a crucial prognostic marker for these conditions.METHODS: Total proteolytic activity was determined using casein as a substrate. To measure the activity of metal-dependent and serine proteases, ethylenediaminetetraacetic acid and phenylmethylsulfonyl fluoride were used. The content of low- and middle-molecular-weight (LMMW) substances was determined spectrophotometrically. The protein profile was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), while zymography was performed to indicate the molecular weight of active enzymes.RESULTS: The pathogenesis of both pancreatic disorders was found to be accompanied by a proteolytic imbalance in pancreatic tissues, manifested in either the increase in the total proteolytic activity under pancreatitis or the decrease in the total proteolytic activity under pancreatic cancer. The increase in the levels of both metal-dependent and serine proteases was indicated in the blood plasma of patients in both studied groups. This proteolytic imbalance was accompanied by the accumulation of protein degradation fragments and LMMW substances. Results of zymography were also informative: pancreatic tissue and plasma samples from patients with either CP or PC were characterized by the presence of additional bands, indicating altered proteolytic activity in both pathological conditions.CONCLUSIONS: This study underscores the importance of proteolytic features in distinguishing CP and PC, offering potential diagnostic markers. Proteolytic shifts may aid in differentiating pathologies, detecting transitions, and developing specific protease inhibitors. Further research is crucial for advancing diagnostic and therapeutic strategies for CP and PC.