Černe Katarina, Kelhar Nuša, Resnik Nataša, Herzog Maruša, Vodnik Lana, Veranič Peter, Kobal Borut
Institute of Pharmacology and Experimental Toxicology, Faculty of Medicine, University of Ljubljana, SI-1000 Ljubljana, Slovenia.
Institute of Cell Biology, Faculty of Medicine, University of Ljubljana, SI-1000 Ljubljana, Slovenia.
Pharmaceuticals (Basel). 2023 Jun 20;16(6):907. doi: 10.3390/ph16060907.
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.
铂耐药高级别浆液性卵巢癌（HGSOC）始终是一种致命疾病。因此，卵巢癌研究的一个核心目标是开发新策略来克服铂耐药性。治疗正朝着个性化疗法发展。然而，仍缺乏可验证的预测患者发生铂耐药风险的分子生物标志物。细胞外囊泡（EVs）是很有前景的候选生物标志物。EpCAM特异性EVs在很大程度上是尚未被探索的预测化疗耐药性的生物标志物。我们使用透射电子显微镜、纳米颗粒跟踪分析和流式细胞术，比较了源自临床确诊的顺铂耐药患者的细胞系（OAW28）释放的EVs与源自对铂类化疗敏感的肿瘤的两个细胞系（PEO1和OAW42）释放的EVs的特征。我们证明，化疗耐药患者的HGSOC细胞系释放的EVs表现出更大的大小异质性、更大比例的中/大（>200 nm）EVs以及更高数量的不同大小的EpCAM阳性EVs释放，尽管EpCAM的表达在大于400 nm的EVs中占主导。我们还发现EpCAM阳性EVs的浓度与细胞EpCAM的表达之间存在强正相关。这些结果可能有助于未来对铂耐药性的预测，尽管首先应在临床样本中进行验证。
