Analysis of Several Pathways for Efficient Killing of Prostate Cancer Stem Cells: A Central Role of NF-κB RELA

Witte K, Pfitzenmaier J, Storm J, Lütkemeyer M, Wimmer C, Schulten W, Czaniera N, Geisler M, Förster C, Wilkens L, Knabbe C, et al. (2021)
International Journal of Molecular Sciences 22(16): 8901.

Zeitschriftenaufsatz | Veröffentlicht | Englisch
 
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Witte, KayaUniBi; Pfitzenmaier, Jesco; Storm, Jonathan; Lütkemeyer, Melanie; Wimmer, Clara; Schulten, Wiebke; Czaniera, Nele; Geisler, Marvin; Förster, Christine; Wilkens, Ludwig; Knabbe, CorneliusUniBi; Mertzlufft, Fritz
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Abstract / Bemerkung
Prostate cancer is a common cause of death worldwide. Here, we isolated cancer stem cells (CSCs) from four adenocarcinomas of the prostate (Gleason scores from 3 + 3 up to 4 + 5). CSCs were characterized by the expression of the stem cell markers TWIST, the epithelial cell adhesion molecule (EPCAM), the transcription factors SNAI1 (SNAIL) and SNAI2 (SLUG) and cancer markers such as CD44 and prominin-1 (CD133). All investigated CSC populations contained a fraction highly positive for aldehyde dehydrogenase (ALDH) function and displayed robust expressions of programmed cell death 1 (PD-1) ligands. Furthermore, we investigated immunotherapeutic approaches but had no success even with the clinically used PD-1 inhibitor pembrolizumab. In addition, we studied another death-inducing pathway via interferon gamma signaling and detected high-level upregulations of human leukocyte antigen A (HLA-A) and beta 2-microglobulin (B2M) with only moderate killing efficacy. To examine further killing mechanisms in prostate cancer stem cells (PCSCs), we analyzed NF-κB signaling. Surprisingly, two patient-specific populations of PCSCs were found: one with canonical NF-κB signaling and another one with blunted NF-κB activation, which can be efficiently killed by tumor necrosis factor (TNF). Thus, culturing of PCSCs and analysis of respective NF-κB induction potency after surgery might be a powerful tool for optimizing patient-specific treatment options, such as the use of TNF-inducing chemotherapeutics and/or NF-κB inhibitors.
Stichworte
prostate cancer; cancer stem cells; nuclear factor “kappa-light-chain-enhancer” of acti-vated B-cells; tumor necrosis factor; interferon gamma; immune checkpoint therapy; programmedcell death 1 ligand 1 and -ligand 2; natural killer cells; major histocompatibility complex class
Erscheinungsjahr
2021
Zeitschriftentitel
International Journal of Molecular Sciences
Band
22
Ausgabe
16
Art.-Nr.
8901
eISSN
1422-0067
Finanzierungs-Informationen
Open-Access-Publikationskosten wurden durch die Universität Bielefeld gefördert.
Page URI
https://pub.uni-bielefeld.de/record/2956862

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Witte K, Pfitzenmaier J, Storm J, et al. Analysis of Several Pathways for Efficient Killing of Prostate Cancer Stem Cells: A Central Role of NF-κB RELA. International Journal of Molecular Sciences. 2021;22(16): 8901.
Witte, K., Pfitzenmaier, J., Storm, J., Lütkemeyer, M., Wimmer, C., Schulten, W., Czaniera, N., et al. (2021). Analysis of Several Pathways for Efficient Killing of Prostate Cancer Stem Cells: A Central Role of NF-κB RELA. International Journal of Molecular Sciences, 22(16), 8901. https://doi.org/10.3390/ijms22168901
Witte, K., Pfitzenmaier, J., Storm, J., Lütkemeyer, M., Wimmer, C., Schulten, W., Czaniera, N., Geisler, M., Förster, C., Wilkens, L., et al. (2021). Analysis of Several Pathways for Efficient Killing of Prostate Cancer Stem Cells: A Central Role of NF-κB RELA. International Journal of Molecular Sciences 22:8901.
Witte, K., et al., 2021. Analysis of Several Pathways for Efficient Killing of Prostate Cancer Stem Cells: A Central Role of NF-κB RELA. International Journal of Molecular Sciences, 22(16): 8901.
K. Witte, et al., “Analysis of Several Pathways for Efficient Killing of Prostate Cancer Stem Cells: A Central Role of NF-κB RELA”, International Journal of Molecular Sciences, vol. 22, 2021, : 8901.
Witte, K., Pfitzenmaier, J., Storm, J., Lütkemeyer, M., Wimmer, C., Schulten, W., Czaniera, N., Geisler, M., Förster, C., Wilkens, L., Knabbe, C., Mertzlufft, F., Kaltschmidt, B., am Esch, J.S., Kaltschmidt, C.: Analysis of Several Pathways for Efficient Killing of Prostate Cancer Stem Cells: A Central Role of NF-κB RELA. International Journal of Molecular Sciences. 22, : 8901 (2021).
Witte, Kaya, Pfitzenmaier, Jesco, Storm, Jonathan, Lütkemeyer, Melanie, Wimmer, Clara, Schulten, Wiebke, Czaniera, Nele, Geisler, Marvin, Förster, Christine, Wilkens, Ludwig, Knabbe, Cornelius, Mertzlufft, Fritz, Kaltschmidt, Barbara, am Esch, Jan Schulte, and Kaltschmidt, Christian. “Analysis of Several Pathways for Efficient Killing of Prostate Cancer Stem Cells: A Central Role of NF-κB RELA”. International Journal of Molecular Sciences 22.16 (2021): 8901.
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