Exosomes in Plasma of Patients with Ovarian Carcinoma: Potential Biomarkers of Tumor Progression and Response to Therapy.
BACKGROUND
In patients with Ovarian Cancer (OvCa) exosomes released by tumor cells are present in the plasma and could be involved in tumor progression. This study examines the association between the exosome presence/protein content in plasma of OvCa patients and disease outcome, response to standard therapy and/or tumorresistance to therapies in patients studied at diagnosis and also serially during and after therapy.


METHODS
Exosomes were purified from OvCa patients' plasma (n=22), patients with benign tumors (n=10) or (n=10) healthy controls (NC) using ultracentrifugation. Exosomes were visualized by scanning electron microscopy. Their protein content was measured. The presence of MAGE 3/6 and TGF-β1 in exosomes was evaluated in Western blots.


RESULTS
The OvCa patients' plasma contained higher levels of exosomal proteins (p<0.05) compared to those isolated from plasma of patients with benign tumors or NC. Exosomes isolated from OvCa patients's plasma carried TGF-β1 and MAGE3/6, which distinguished OvCa patients from those with benign tumors and NC. High protein levels of exosomes were seen in newly diagnosed patients; however in advanced stages of OvCa patients the protein content of isolated exosomes was significantly higher than that of early stages. The exosome levels variably changed during/after chemotherapy, and correlations between the changes in exosomal protein levels and clinical data suggested that the protein content of exosomes might be useful in predicting responses to therapy and prognosis in OvCa patients.


CONCLUSIONS
Analysis of plasma exosomes levels offers a novel approach to diagnosis and monitoring response to therapies in OvCa patients.
Departments of Gynecology Oncology, Military Institute of Medicine, Warsaw, Poland ; Department of Gynecology and Gynecologic Oncology, Military Institute of Medicine, Warsaw, Poland.
Marta
M
Szajnik
Department of Clinical Immunology Military Institute of Medicine, Warsaw, Poland.
Magdalena
M
Derbis
Department of Clinical Immunology Military Institute of Medicine, Warsaw, Poland.
Michal
M
Lach
Department of Clinical Immunology Military Institute of Medicine, Warsaw, Poland.
Paulina
P
Patalas
Departments of Gynecology Oncology, Military Institute of Medicine, Warsaw, Poland.
Marcin
M
Michalak
Department of Biochemistry and Molecular Biology, Military Institute of Medicine, Warsaw, Poland.
Hanna
H
Drzewiecka
Division of Gynecology Surgery, Poznan University of Medical Sciences, 61-701 Poznan, Poland.
Dariusz
D
Szpurek
Department of Gynecology and Gynecologic Oncology, Military Institute of Medicine, Warsaw, Poland.
Andrzej
A
Nowakowski
Departments of Gynecology Oncology, Military Institute of Medicine, Warsaw, Poland.
Marek
M
Spaczynski
Department of Gynecology and Gynecologic Oncology, Military Institute of Medicine, Warsaw, Poland.
Włodzimierz
W
Baranowski
University of Pittsburgh Cancer Institute, Pittsburgh, PA, 15213, USA.
Theresa L
TL
Whiteside
Exosomes; Ovarian carcinoma; Prognosis; Response to therapy