Pre-existing cell subpopulations in primary prostate cancer tumors display surface fingerprints of docetaxel-resistant cells

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Publikace nespadá pod Fakultu sportovních studií, ale pod Přírodovědeckou fakultu. Oficiální stránka publikace je na webu muni.cz.
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DRÁPELA Stanislav KVOKAČKOVÁ Barbora SLABÁKOVÁ Eva VYHLÍDALOVÁ KOTRBOVÁ Anna GÖMÖRYOVÁ Kristína FEDR Radek KURFUERSTOVA Daniela ELIAS Martin STUDENT Vladimir LENCESOVA Frederika GANJI Sri Ranjani HLAVÁČKOVÁ POSPÍCHALOVÁ Vendula BRYJA Vítězslav VAN WEERDEN Wytske M PUHR Martin CULIG Zoran BOUCHAL Jan SOUCEK Karel

Rok publikování 2024
Druh Článek v odborném periodiku
Časopis / Zdroj CELLULAR ONCOLOGY
Fakulta / Pracoviště MU

Přírodovědecká fakulta

Citace
www https://link.springer.com/article/10.1007/s13402-024-00982-2
Doi http://dx.doi.org/10.1007/s13402-024-00982-2
Klíčová slova Prostate cancer; Docetaxel resistance; Intratumoral heterogeneity; Plasticity; CD95/Fas; SSEA-4
Přiložené soubory
Popis PurposeDocetaxel 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.MethodsTo 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.ResultsOur 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.ConclusionIn 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.
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