Exosomes in Plasma of Patients with Ovarian Carcinoma: Potential Biomarkers of Tumor Progression and Response to Therapy

Abstract

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. Design and 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. Conclusion: Analysis of plasma exosomes levels offers a novel approach to diagnosis and monitoring response to therapies in OvCa patients.

Exosomal microRNA Biomarkers: Emerging Frontiers in Colorectal and Other Human Cancers

“…However, since the recognition that exosomes have tissue and/or organ-specificity combined with their easy detection in serum, it is becoming increasingly attractive to exploit their potential as cancer biomarkers. Fortunately, another school of thought favoring this rationale is that cancer cells appear to secrete larger quantities of exosomes vis-à-vis normal cells [74,75]. Although the underlying mechanisms for this disparate secretion of exosomes in cancer vs. normal cells remains unclear, it is believed that the low pH associated with the tumor microenvironment favors production of exosomes in cancer cells and their subsequent uptake or fusion by the target cells [76,77].…”

Miniaturized Biomedical Sensors for Enumeration of Extracellular Vesicles

“…The dynamic range of detection exhibited by our GaN HEMT sensor is comparable to the gold standard EV detection methodology of nanoparticle tracking analysis (10 7 –10 10 EVs/mL). Enumeration of EVs has the potential for risk assessment of cardiovascular diseases like coronary artery disease and early diagnosis of several types of cancers such as ovarian, lung and gastric cancer [23,24,25,26,27]. Therefore, our electronic microsensor has the potential to improve point of care diagnostics for diseases that cause the largest mortality worldwide.…”

Extracellular vesicles as emerging targets in cancer: Recent development from bench to bedside

“…The exosome concentration in plasma has been reported to be 10 9 –10 11 exosome/ml (269, 270). When translated into protein, serum and plasma have the concentrations at 50–200 μg/ml while freeze-thaw can increase the concentration to 50–500 μg/ml (269, 271). Thus, exosome treatment should ensure that the concentration used is within the physiological range.…”