Jian Zheng1, Jonathan M Hernandez1, Alexandre Doussot1, Linda Bojmar2, Constantinos P Zambirinis1, Bruno Costa-Silva2, Elke J A H van Beek2, Milica T Mark3, Henrik Molina3, Gokce Askan4, Olca Basturk4, Mithat Gonen5, T Peter Kingham1, Peter J Allen1, Michael I D'Angelica1, Ronald P DeMatteo1, David Lyden2, William R Jarnagin6. 1. Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA. 2. Children's Cancer and Blood Foundation Laboratories, Department of Pediatrics, Drukier Institute for Children's Health, Meyer Cancer Center, Weill Cornell Medical College, New York, NY, USA; Department of Cell and Developmental Biology, Drukier Institute for Children's Health, Meyer Cancer Center, Weill Cornell Medical College, New York, NY, USA. 3. Proteomics Resource Center, The Rockefeller University, New York, NY, USA. 4. Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA. 5. Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA. 6. Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA. Electronic address: jarnagiw@mskcc.org.
Abstract
BACKGROUND: Exosomes are nanovesicles that have been shown to mediate carcinogenesis in pancreatic ductal adenocarcinoma (PDAC). Given the direct communication of pancreatic duct fluid with the tumor and its relative accessibility, we aimed to determine the feasibility of isolating and characterizing exosomes from pancreatic duct fluid. METHODS: Pancreatic duct fluid was collected from 26 patients with PDAC (n = 13), intraductal papillary mucinous neoplasm (IPMN) (n = 8) and other benign pancreatic diseases (n = 5) at resection. Exosomes were isolated by serial ultracentrifugation, proteins were identified by mass spectrometry, and their expression was evaluated by immunohistochemistry. RESULTS: Exosomes were isolated from all specimens with a mean concentration of 5.9 ± 1 × 108 particles/mL and most frequent size of 138 ± 9 nm. Among the top 35 proteins that were significantly associated with PDAC, multiple carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) and extracellular matrix (ECM) proteins were identified. Interestingly, CEACAM 1/5 expression by immunohistochemistry was seen only on tumor epithelia whereas tenascin C positivity was restricted to stroma, suggesting that both tumor and stromal cells contributed to exosomes. CONCLUSION: This is the first study showing that exosome isolation is feasible from pancreatic duct fluid, and that exosomal proteins may be utilized to diagnose patients with PDAC.
BACKGROUND: Exosomes are nanovesicles that have been shown to mediate carcinogenesis in pancreatic ductal adenocarcinoma (PDAC). Given the direct communication of pancreatic duct fluid with the tumor and its relative accessibility, we aimed to determine the feasibility of isolating and characterizing exosomes from pancreatic duct fluid. METHODS:Pancreatic duct fluid was collected from 26 patients with PDAC (n = 13), intraductal papillary mucinous neoplasm (IPMN) (n = 8) and other benign pancreatic diseases (n = 5) at resection. Exosomes were isolated by serial ultracentrifugation, proteins were identified by mass spectrometry, and their expression was evaluated by immunohistochemistry. RESULTS: Exosomes were isolated from all specimens with a mean concentration of 5.9 ± 1 × 108 particles/mL and most frequent size of 138 ± 9 nm. Among the top 35 proteins that were significantly associated with PDAC, multiple carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) and extracellular matrix (ECM) proteins were identified. Interestingly, CEACAM 1/5 expression by immunohistochemistry was seen only on tumor epithelia whereas tenascin C positivity was restricted to stroma, suggesting that both tumor and stromal cells contributed to exosomes. CONCLUSION: This is the first study showing that exosome isolation is feasible from pancreatic duct fluid, and that exosomal proteins may be utilized to diagnose patients with PDAC.
Authors: Sam C Wang; Justin R Parekh; Matthew R Porembka; Hari Nathan; Michael I D'Angelica; Ronald P DeMatteo; Yuman Fong; T Peter Kingham; William R Jarnagin; Peter J Allen Journal: J Gastrointest Surg Date: 2016-02-26 Impact factor: 3.452
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Authors: Mara H Sherman; Ruth T Yu; Tiffany W Tseng; Cristovao M Sousa; Sihao Liu; Morgan L Truitt; Nanhai He; Ning Ding; Christopher Liddle; Annette R Atkins; Mathias Leblanc; Eric A Collisson; John M Asara; Alec C Kimmelman; Michael Downes; Ronald M Evans Journal: Proc Natl Acad Sci U S A Date: 2017-01-17 Impact factor: 11.205
Authors: Diane M Simeone; Baoan Ji; Mousumi Banerjee; Thiruvengadam Arumugam; Dawei Li; Michelle A Anderson; Ann Marie Bamberger; Joel Greenson; Randal E Brand; Vijaya Ramachandran; Craig D Logsdon Journal: Pancreas Date: 2007-05 Impact factor: 3.327
Authors: Dylan Nicholas Tabang; Yusi Cui; Daniel M Tremmel; Megan Ford; Zihui Li; Sara Dutton Sackett; Jon S Odorico; Lingjun Li Journal: Mol Omics Date: 2021-10-11