2024
Drápela, Stanislav; Kvokačková, Barbora; Slabáková, Eva; Kotrbová, Anna; Gömöryová, Kristína; Fedr, Radek; Kurfürstová, Daniela; Eliáš, Martin; Študent, Vladimír Jr; Lenčéšová, Frederika; Ranjani, Ganji Sri; Pospíchalová, Vendula; Bryja, Vítězslav; Weerden, Wytske M.; Puhr, Martin; Culig, Zoran; Bouchal, Jan; Souček, Karel
Pre-existing cell subpopulations in primary prostate cancer tumors display surface fingerprints of docetaxel-resistant cells. Journal Article
In: Cellular oncology (Dordrecht, Netherlands), 2024, ISSN: 2211-3436 2211-3428, (Place: Netherlands).
Abstract | Links | BibTeX | Tags: CD95/Fas, Docetaxel resistance, Intratumoral heterogeneity, Plasticity, Prostate cancer, SSEA-4
@article{drapela_pre-existing_2024,
title = {Pre-existing cell subpopulations in primary prostate cancer tumors display surface fingerprints of docetaxel-resistant cells.},
author = {Stanislav Drápela and Barbora Kvokačková and Eva Slabáková and Anna Kotrbová and Kristína Gömöryová and Radek Fedr and Daniela Kurfürstová and Martin Eliáš and Vladimír Jr Študent and Frederika Lenčéšová and Ganji Sri Ranjani and Vendula Pospíchalová and Vítězslav Bryja and Wytske M. Weerden and Martin Puhr and Zoran Culig and Jan Bouchal and Karel Souček},
doi = {10.1007/s13402-024-00982-2},
issn = {2211-3436 2211-3428},
year = {2024},
date = {2024-08-01},
journal = {Cellular oncology (Dordrecht, Netherlands)},
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.},
note = {Place: Netherlands},
keywords = {CD95/Fas, Docetaxel resistance, Intratumoral heterogeneity, Plasticity, Prostate cancer, SSEA-4},
pubstate = {published},
tppubtype = {article}
}
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.