Pre-existing cell subpopulations in primary prostate cancer tumors display surface fingerprints of docetaxel-resistant cells
Year: 2024
Type: article
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.
Source: Cellular Oncology
Authors: Stanislav Drápela, Barbora Kvokačková, Eva Slabáková, Anna Kotrbová, Kristína Gömöryová, Radek Fedr, Daniela Kurfürstová, Martin Eliáš, Vladimír Študent jr, Frederika Lenčéšová, Ganji Sri Ranjani, Vendula Pospíchalová, Vítězslav Bryja, Wytske M. van Weerden, Martin Puhr, Zoran Culig, Jan Bouchal, Karel Souček
Institutions: Masaryk University, Moffitt Cancer Center, Czech Academy of Sciences, Institute of Biophysics, International Clinical Research Center, St. Anne's University Hospital Brno, St. Anne's University Hospital Brno, University Hospital Olomouc, Institute of Molecular and Translational Medicine, Palacký University Olomouc, Central European Institute of Technology – Masaryk University, Erasmus MC, Erasmus MC Cancer Institute, Innsbruck Medical University, Universität Innsbruck
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $4,390
OpenAlex ID: W4401715367