TitleA Preliminary Proteomic Investigation of Circulating Exosomes and Discovery of Biomarkers Associated with the Progression of Osteosarcoma in a Clinical Model of Spontaneous Disease.
Publication TypeJournal Article
Year of Publication2018
AuthorsBrady, JV, Troyer, RM, Ramsey, SA, Leeper, H, Yang, L, Maier, CS, Goodall, CP, Ruby, CE, Albarqi, HAM, Taratula, O, Bracha, S
JournalTransl Oncol
Volume11
Issue5
Pagination1137-1146
Date Published2018 Oct
ISSN1936-5233
Abstract

Circulating cancer exosomes are microvesicles which originate from malignant cells and other organs influenced by the disease and can be found in blood. The exosomal proteomic cargo can often be traced to the cells from which they originated, reflecting the physiological status of these cells. The similarities between cancer exosomes and the tumor cells they originate from exhibit the potential of these vesicles as an invaluable target for liquid biopsies. Exosomes were isolated from the serum of eight osteosarcoma-bearing dogs, five healthy dogs, and five dogs with traumatic fractures. We also characterized exosomes which were collected longitudinally from patients with osteosarcoma prior and 2 weeks after amputation, and eventually upon detection of lung metastasis. Exosomal proteins fraction were analyzed by label-free mass spectrometry proteomics and were validated with immunoblots of selected proteins. Ten exosomal proteins were found that collectively discriminate serum of osteosarcoma patients from serum healthy or fractured dogs with an accuracy of 85%. Additionally, serum from different disease stages could be distinguished with an accuracy of 77% based on exosomal proteomic composition. The most discriminating protein changes for both sample group comparisons were related to complement regulation, suggesting an immune evasion mechanism in early stages of osteosarcoma as well as in advanced disease.

DOI10.1016/j.tranon.2018.07.004
Alternate JournalTransl Oncol
PubMed ID30053712
PubMed Central IDPMC6077151
Grant ListS10 OD020111 / OD / NIH HHS / United States