Abstract
Purpose: Pancreatic cancer is one of the most lethal of solid tumors and is associated with aggressive cancer biology. The purpose is to review the role of trypsin and effect on molecular and cellular processes potentially explaining the aggressive biology in pancreatic cancer.Methods: A narrative literature review of studies investigating trypsin and its effect on protease systems in cancer, with special reference to pancreatic cancer biology.Results: Proteases, such as trypsin, provides a significant advantage to developing tumors through the ability to remodel the extracellular matrix, promote cell invasion and migration, and facilitate angiogenesis. Trypsin is a digestive enzyme produced by the exocrine pancreas that is also related to mechanisms of proliferation, invasion and metastasis. Several of these mechanisms may be co-regulated or influenced by activation of proteinase-activated receptor 2 (PAR-2). The current role in pancreatic cancer is not clear but emerging data suggest several potential mechanisms. Trypsin may act as a Trojan horse in the pancreatic gland, facilitating several molecular pathways from the onset, which leads to rapid progression of the disease. Pancreatic cancer cell lines containing PAR-2 proliferate upon exposure to trypsin, whereas cancer cell lines not containing PAR-2 fail to proliferate upon trypsin expression. Several mechanisms of action include a proinflammatory environment, signals inducing proliferation and migration, and direct and indirect evidence for mechanisms promoting invasion and metastasis. Novel techniques (such as organoid models) and increased understanding of mechanisms (such as the microbiome) may yield improved understanding into the role of trypsin in pancreatic carcinogenesis.Conclusion: Trypsin is naturally present in the pancreatic gland and may experience pathological activation intracellularly and in the neoplastic environment, which speeds up molecular mechanisms of proliferation, invasion, and metastasis. Further investigation of these processes will provide important insights into how pancreatic cancer evolves, and suggest new ways for treatment.
Highlights
Pancreatic cancer is one of the most lethal solid organ tumors and is estimated to become one of the top two leading causes to cancer deaths within the decade.[1]Patients with pancreatic cancer experience a very poor survival with 5 years after diagnosis
This study found the increased pancreatic juice expression to be related to IPMNs only and the expression of trypsin per se was not investigated, it would suggest that the inhibitor is increased in either a response to increased trypsin activity or acts as an upregulated protein by itself and, acts as a pro-neoplastic factor
Trypsin leakage causes cellular proliferation in pancreatitis Trypsin expression is found to be increased in pancreatic precursors, such as IPMNs Indolent tumors of the pancreas, such as intraductal tubulopapillary neoplasm of the pancreas (ITNP), does not stain for trypsin Several factors that may be activated by trypsin, including proteinaseactivated receptor 2 (PAR-2) and
Summary
Pancreatic cancer is one of the most lethal solid organ tumors and is estimated to become one of the top two leading causes to cancer deaths within the decade.[1]. Speaking, a ‘‘Trojan Horse’’ has come to mean any trick or stratagem that causes a target to invite a foe into a securely protected bastion or place, or; refers to subversion introduced from the outside; or, more recently, applied to deceptively benign computer codes that seem like legitimate applications but are written to damage or disrupt a computer program Trypsin, it seems, may have the above capabilities to circumvent a siege to a full-blown attack in pancreatic cancer. The premature activation or, even intracellular activation, of other types of proteases has been demonstrated to be important mechanism to disease states through mechanisms hitherto poorly understood or scarcely investigated.[9] Premature release and activation in the cell or leaks of trypsin into the stroma may facilitate activation of enzyme cascades, leading to cellular proliferation, migration, invasion, angiogenesis, and metastasis (Fig. 1). Trypsin may help explain why pancreas cancer is among the most lethal, aggressive form of human cancers, usually presents at a locally advanced stage at time of diagnosis, with an invasive and metastatic nature unfamiliar to most other solid organ cancers.[15]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
