Characteristics of Extracellular Vesicles from a High-Grade Serous Ovarian Cancer Cell Line Derived from a Platinum-Resistant Patient as a Potential Tool for Aiding the Prediction of Responses to Chemotherapy

Katarina Černe; Nuša Kelhar; Nataša Resnik; Maruša Herzog; Lana Vodnik; Peter Veranič; Borut Kobal

doi:10.3390/ph16060907

Characteristics of Extracellular Vesicles from a High-Grade Serous Ovarian Cancer Cell Line Derived from a Platinum-Resistant Patient as a Potential Tool for Aiding the Prediction of Responses to Chemotherapy

Pharmaceuticals (Basel). 2023 Jun 20;16(6):907. doi: 10.3390/ph16060907.

Authors

Katarina Černe¹, Nuša Kelhar¹, Nataša Resnik², Maruša Herzog^{3

4}, Lana Vodnik¹, Peter Veranič², Borut Kobal^{3

4}

Affiliations

¹ Institute of Pharmacology and Experimental Toxicology, Faculty of Medicine, University of Ljubljana, SI-1000 Ljubljana, Slovenia.
² Institute of Cell Biology, Faculty of Medicine, University of Ljubljana, SI-1000 Ljubljana, Slovenia.
³ Division of Gynecology and Obstetrics, University Medical Centre Ljubljana, SI-1000 Ljubljana, Slovenia.
⁴ Department of Gynecology and Obstetrics, Faculty of Medicine, University Ljubljana, SI-1000 Ljubljana, Slovenia.

Abstract

Platinum-resistant high-grade serous ovarian cancer (HGSOC) is invariably a fatal disease. A central goal of ovarian cancer research is therefore to develop new strategies to overcome platinum resistance. Treatment is thus moving towards personalized therapy. However, validated molecular biomarkers that predict patients' risk of developing platinum resistance are still lacking. Extracellular vesicles (EVs) are promising candidate biomarkers. EpCAM-specific EVs are largely unexplored biomarkers for predicting chemoresistance. Using transmission electron microscopy, nanoparticle tracking analysis and flow cytometry, we compared the characteristics of EVs released from a cell line derived from a clinically confirmed cisplatin-resistant patient (OAW28) and EVs released from two cell lines from tumors sensitive to platinum-based chemotherapy (PEO1 and OAW42). We demonstrated that EVs released from the HGSOC cell line of chemoresistant patients exhibited greater size heterogeneity, a larger proportion of medium/large (>200 nm) Evs and a higher number of released EpCAM-positive EVs of different sizes, although the expression of EpCAM was predominant in EVs larger than 400 nm. We also found a strong positive correlation between the concentration of EpCAM-positive EVs and the expression of cellular EpCAM. These results may contribute to the prediction of platinum resistance in the future, although they should first be validated in clinical samples.

Keywords: EpCAM; HGSOC; cell lines; chemoresistance; extracellular vesicles.

Grants and funding

This research was supported by the Slovenian Research Agency via the research programs P3-067, J3-2521 and P3-0108 and by the University Medical Centre Ljubljana (Project Number: 20180033).