TY  - JOUR
AB  - 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.
DA  - 2021
DO  - 10.3390/ijms22168901
KW  - prostate cancer
KW  - cancer stem cells
KW  - nuclear factor “kappa-light-chain-enhancer” of acti-vated B-cells
KW  - tumor necrosis factor
KW  - interferon gamma
KW  - immune checkpoint therapy
KW  - programmedcell death 1 ligand 1 and -ligand 2
KW  - natural killer cells
KW  - major histocompatibility complex class
LA  - eng
IS  - 16
PY  - 2021
T2  - International Journal of Molecular Sciences
TI  - Analysis of Several Pathways for Efficient Killing of Prostate Cancer Stem Cells: A Central Role of NF-κB RELA
UR  - https://nbn-resolving.org/urn:nbn:de:0070-pub-29568625
Y2  - 2024-11-21T22:00:32
ER  -