Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Characteristics of Extracellular Vesicles From an HGSOC Cell Line Derived From a Platinum-Resistant Patient as a Potential Tool for Aiding Prediction of Response to Chemotherapy

Version 1 : Received: 3 May 2023 / Approved: 4 May 2023 / Online: 4 May 2023 (05:18:59 CEST)

A peer-reviewed article of this Preprint also exists.

Černe, K.; Kelhar, N.; Resnik, N.; Herzog, M.; Vodnik, L.; Veranič, P.; Kobal, B. 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 2023, 16, 907. Černe, K.; Kelhar, N.; Resnik, N.; Herzog, M.; Vodnik, L.; Veranič, P.; Kobal, B. 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 2023, 16, 907.

Abstract

Platinum-resistant high-grade serous ovarian cancer (HGSOC) is invariably a fatal disease, so a central goal in ovarian cancer research is to develop novel strategies to overcome platinum resistance. Treatment is thus moving towards personalized therapy. However, validated molecular biomarkers to predict patients’ risk of developing platinum resistance are still lacking. Extracellular vesicles (EVs) are promising candidates for biomarkers. EpCAM-specific EVs are largely unexplored biomarkers in 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, OAW42). We showed that characteristics of EVs released from the HGSOC cell line of chemoresistant patients had higher heterogeneity in size, a larger proportion of medium/large (>200nm) EVs and a higher number of released EpCAM-positive EVs of different sizes, although expression of EpCAM predominated, especially on those larger than 400 nm. We also determined a strong positive correlation between the concentration of EpCAM-positive EVs and expression of cellular EpCAM. These results may contribute to prediction of platinum resistance in the future, although they should first be validated in clinical samples.

Keywords

cell lines; chemoresistance; EpCAM; extracellular vesicles; HGSOC 1

Subject

Medicine and Pharmacology, Obstetrics and Gynaecology

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