The lysosomal aminopeptidase tripeptidyl peptidase 1 displays increased activity in malignant pancreatic cysts
| Autor: | Kimberly S. Kirkwood, Sam L. Ivry, Charles S. Craik, Francesco Caiazza, Matthew Ravalin, Jeremy Sharib, Anthony J. O’Donoghue, Giselle M. Knudsen, Katrin Jaradeh |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Proteomics Pathology medicine.medical_specialty medicine.medical_treatment Clinical Biochemistry Biochemistry Aminopeptidase Aminopeptidases Tripeptidyl peptidase 03 medical and health sciences 0302 clinical medicine Pancreatic cancer parasitic diseases medicine Humans Cyst Dipeptidyl-Peptidases and Tripeptidyl-Peptidases Molecular Biology Protease biology Tripeptidyl-Peptidase 1 business.industry Exopeptidase medicine.disease Pancreatic Neoplasms 030104 developmental biology Dysplasia 030220 oncology & carcinogenesis biology.protein Pancreatic cysts Pancreatic Cyst Serine Proteases business Lysosomes |
| Zdroj: | Biological chemistryReferences. 400(12) |
| ISSN: | 1437-4315 |
| Popis: | Incidental detection of pancreatic cysts has increased dramatically over the last decade, but risk stratification and clinical management remain a challenge. Mucinous cysts are precursor lesions to pancreatic cancer, however, the majority are indolent. Current diagnostics cannot identify mucinous cysts that harbor cancer or reliably differentiate these lesions from nonmucinous cysts, which present minimal risk of malignant progression. We previously determined that activity of two aspartyl proteases was increased in mucinous cysts. Using a global protease activity profiling technology, termed multiplex substrate profiling by mass spectrometry (MSP-MS), we now show that aminopeptidase activity is also elevated in mucinous cysts. The serine aminopeptidase, tripeptidyl peptidase 1 (TPP1), was detected by proteomic analysis of cyst fluid samples and quantitation using targeted MS demonstrated that this protease was significantly more abundant in mucinous cysts. In a cohort of 110 cyst fluid samples, TPP1 activity was increased more than 3-fold in mucinous cysts relative to nonmucinous cysts. Moreover, TPP1 activity is primarily associated with mucinous cysts that harbor high-grade dysplasia or invasive carcinoma. Although only 59% accurate for differentiating these lesions, measurement of TPP1 activity may improve early detection and treatment of high-risk pancreatic cysts when used in conjunction with other promising biomarkers. |
| Databáze: | OpenAIRE |
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