Circulating exosomes are biomarkers for chemotherapy-induced tissue injury

Exosomes, nanovesicles released from most cell types to extracellular compartments, are abundant in systemic circulation [1]. Exosome release is induced by stress conditions including oxidative stress [2,3]. Nearly 50% of FDA-approved chemotherapeutic drugs cause oxidative stress leading to long-term side effects and damage to non-targeted tissues, including heart, brain, liver and skeletal muscle [4]. The tissue of origin and contents of circulating exosomes during chemotherapy treatment are unknown. Here, we demonstrate that Doxorubicin (DOX) caused a two-fold increase in circulating exosomes (DOX_EXO) compared to saline-treated exosomes (SAL_EXO) in an experimental therapeutic model. Proteomic analysis of mouse serum exosomes identified DOX- dependent, tissue-specific proteins glycogen phosphorylase brain form (PYGB), muscle form (PYGM) and liver form (PYGL), which are specific to heart, brain, skeletal muscle, and liver. The presence of PYGB only in DOX_EXO is consistent with observed cardiac dysfunction in DOX treated mice. We also found that PYGB, PYGM and PYGL tended to increase in serum exosomes of cancer patients within three weeks of DOX treatment. Thus, circulating exosomes are a potential early biomarker for tissue injuries from chemotherapy and may help predict the risk of cancer patients to develop long-term side effects from chemotherapy.

Chontida Yarana1,5, Luksana Chaiswing1, Teresa Noel1, Jing Chen2, Haining Zhu2, Emily Dressler3, Jeffrey Moscow4, and Daret St.Clair1

1. Department of Toxicology and Cancer Biology,
2. Department of Molecular and Cellular Biochemistry,
3. Biostatistics and Bioinformatics Shared Resource Facility, Markey Cancer Center, University of Kentucky,
4. National Cancer Institute, United States,
5. Faculty of Medical Technology, Mahidol University, Thailand

This poster was presented at Circulating Biomarkers World Congress 2016