title: Quantitative Proteomic Analysis of Serum Exosomes from Patients with Locally Advanced Pancreatic Cancer Undergoing Chemoradiotherapy.
abstract: Pancreatic cancer is the third leading cause of cancer-related death in the USA. Despite extensive research, minimal improvements in patient outcomes have been achieved. Early identification of treatment response and metastasis would be valuable to determine the appropriate therapeutic course for patients. In this work, we isolated exosomes from the serum of 10 patients with locally advanced pancreatic cancer at serial time points over a course of therapy, and quantitative analysis was performed using the iTRAQ method. We detected approximately 700-800 exosomal proteins per sample, several of which have been implicated in metastasis and treatment resistance. We compared the exosomal proteome of patients at different time points during treatment to healthy controls and identified eight proteins that show global treatment-specific changes. We then tested the effect of patient-derived exosomes on the migration of tumor cells and found that patient-derived exosomes, but not healthy controls, induce cell migration, supporting their role in metastasis. Our data show that exosomes can be reliably extracted from patient serum and analyzed for protein content. The differential loading of exosomes during a course of therapy suggests that exosomes may provide novel insights into the development of treatment resistance and metastasis.
authors.affiliation: Department of Surgery, University of Michigan Medical Center , Ann Arbor, Michigan 48109, United States.
authors.forename: Mingrui
authors.initials: M
authors.lastname: An
authors.affiliation: Department of Radiation Oncology, University of Michigan , Ann Arbor, Michigan 48109, United States.
authors.forename: Ines
authors.initials: I
authors.lastname: Lohse
authors.affiliation: Department of Surgery, University of Michigan Medical Center , Ann Arbor, Michigan 48109, United States.
authors.forename: Zhijing
authors.initials: Z
authors.lastname: Tan
authors.affiliation: Department of Surgery, University of Michigan Medical Center , Ann Arbor, Michigan 48109, United States.
authors.forename: Jianhui
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Department of Surgery, University of Michigan Medical Center , Ann Arbor, Michigan 48109, United States.
authors.forename: Jing
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Radiation Oncology, University of Michigan , Ann Arbor, Michigan 48109, United States.
authors.forename: Himabindu
authors.initials: H
authors.lastname: Kurapati
authors.affiliation: Department of Radiation Oncology, University of Michigan , Ann Arbor, Michigan 48109, United States.
authors.forename: Meredith A
authors.initials: MA
authors.lastname: Morgan
authors.affiliation: Department of Radiation Oncology, University of Michigan , Ann Arbor, Michigan 48109, United States.
authors.forename: Theodore S
authors.initials: TS
authors.lastname: Lawrence
authors.affiliation: Department of Radiation Oncology, University of Michigan , Ann Arbor, Michigan 48109, United States.
authors.forename: Kyle C
authors.initials: KC
authors.lastname: Cuneo
authors.affiliation: Department of Surgery, University of Michigan Medical Center , Ann Arbor, Michigan 48109, United States.
authors.forename: David M
authors.identifier: 0000-0001-7731-0232
authors.initials: DM
authors.lastname: Lubman
mesh_terms: D001798:Blood Proteins / Q000096:biosynthesis / Q000235:genetics*; D055354:Exosomes / Q000187:drug effects / Q000528:radiation effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000097:blood* / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy; D010190:Pancreatic Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy; D020543:Proteome / Q000235:genetics*
chemical_list: D001798:Blood Proteins; D020543:Proteome
keywords: chemoradiation; chemotherapy; exosomes; iTRAQ; metastasis; pancreatic cancer