Pre-existing cell subpopulations in primary prostate cancer tumors display surface fingerprints of docetaxel-resistant cells
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Published:2024-08-20
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ISSN:2211-3428
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Container-title:Cellular Oncology
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language:en
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Short-container-title:Cell Oncol.
Author:
Drápela Stanislav, Kvokačková Barbora, Slabáková Eva, Kotrbová Anna, Gömöryová Kristína, Fedr Radek, Kurfürstová Daniela, Eliáš Martin, Študent jr Vladimír, Lenčéšová Frederika, Ranjani Ganji Sri, Pospíchalová Vendula, Bryja Vítězslav, van Weerden Wytske M., Puhr Martin, Culig Zoran, Bouchal Jan, Souček KarelORCID
Abstract
Abstract
Purpose
Docetaxel resistance is a significant obstacle in the treatment of prostate cancer (PCa), resulting in unfavorable patient prognoses. Intratumoral heterogeneity, often associated with epithelial-to-mesenchymal transition (EMT), has previously emerged as a phenomenon that facilitates adaptation to various stimuli, thus promoting cancer cell diversity and eventually resistance to chemotherapy, including docetaxel. Hence, understanding intratumoral heterogeneity is essential for better patient prognosis and the development of personalized treatment strategies.
Methods
To address this, we employed a high-throughput single-cell flow cytometry approach to identify a specific surface fingerprint associated with docetaxel-resistance in PCa cells and complemented it with proteomic analysis of extracellular vesicles. We further validated selected antigens using docetaxel-resistant patient-derived xenografts in vivo and probed primary PCa specimens to interrogate of their surface fingerprint.
Results
Our approaches revealed a 6-molecule surface fingerprint linked to docetaxel resistance in primary PCa specimens. We observed consistent overexpression of CD95 (FAS/APO-1), and SSEA-4 surface antigens in both in vitro and in vivo docetaxel-resistant models, which was also observed in a cell subpopulation of primary PCa tumors exhibiting EMT features. Furthermore, CD95, along with the essential enzymes involved in SSEA-4 synthesis, ST3GAL1, and ST3GAL2, displayed a significant increase in patients with PCa undergoing docetaxel-based therapy, correlating with poor survival outcomes.
Conclusion
In summary, we demonstrate that the identified 6-molecule surface fingerprint associated with docetaxel resistance pre-exists in a subpopulation of primary PCa tumors before docetaxel treatment. Thus, this fingerprint warrants further validation as a promising predictive tool for docetaxel resistance in PCa patients prior to therapy initiation.
Funder
Institute of Biophysics of the Czech Academy of Sciences
Publisher
Springer Science and Business Media LLC
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