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bioRxiv · 10.1101/2021.01.28.428577

Pre-existing cell subpopulations in primary prostate cancers display surface fingerprint of docetaxel-resistant cells

Drapela, S.·Kvokackova, B.·Fedr, R.·Kurfurstova, D.·Morong, M.·Student, V.·van Weerden, W. M.·Puhr, M.·Culig, Z.·Bouchal, J.·Soucek, K.
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Abstract

BackgroundDocetaxel resistance represents a leading obstacle in the therapy of prostate cancer (PCa), resulting in lethal disease. Intratumoral heterogeneity, which is frequently driven by epithelial-mesenchymal plasticity significantly contributes to the limited treatment response, chemoresistance, and subsequent poor prognosis of patients with lethal PCa. MethodsWe employed a high-throughput flow cytometry screening to identify cell surface fingerprint that associates with docetaxel resistance in PCa cells. Using patient-derived xenografts, we validated protein expression of the most robustly changed antigens in vivo and further assessed this 6-molecule surface fingerprint in primary PCa tumors. ResultsWe revealed the overexpression of SSEA-4 antigen in both in vitro and in vivo docetaxel-resistant models and confirmed the SSEA-4 enrichment in a subpopulation of freshly isolated primary PCa tumors. The level of ST3GAL2, an enzyme that is critically involved in the SSEA-4 synthesis, correlated with increased expression of CD44, CD59, and CD95 and reduced expression of EpCAM and CD9. SSEA-4 was further directly linked to the antimicrotubule agent resistance and poor prognosis in PCa patients. ConclusionsWe propose that the 6-molecule surface fingerprint associates with docetaxel resistance and pre-exists in a cell subpopulation of primary PCa tumors even before docetaxel treatment.

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Drapela, S., Kvokackova, B., Fedr, R., Kurfurstova, D., Morong, M., Student, V., van Weerden, W. M., Puhr, M., Culig, Z., Bouchal, J., Soucek, K.. 2021-01-28. Pre-existing cell subpopulations in primary prostate cancers display surface fingerprint of docetaxel-resistant cells. https://doi.org/10.1101/2021.01.28.428577

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