| Autor: |
Windmöller BA; Department of Cell Biology, University of Bielefeld, Universitätsstrasse 25, 33615 Bielefeld, Germany.; Forschungsverbund BioMedizin Bielefeld/OWL FBMB e. V., Maraweg 21, 33617 Bielefeld, Germany., Beshay M; Forschungsverbund BioMedizin Bielefeld/OWL FBMB e. V., Maraweg 21, 33617 Bielefeld, Germany.; Department of General Thoracic Surgery, Protestant Hospital of Bethel Foundation, Burgsteig 13, 33617 Bielefeld, Germany., Helweg LP; Department of Cell Biology, University of Bielefeld, Universitätsstrasse 25, 33615 Bielefeld, Germany.; Forschungsverbund BioMedizin Bielefeld/OWL FBMB e. V., Maraweg 21, 33617 Bielefeld, Germany., Flottmann C; Department of Cell Biology, University of Bielefeld, Universitätsstrasse 25, 33615 Bielefeld, Germany., Beermann M; Department of Cell Biology, University of Bielefeld, Universitätsstrasse 25, 33615 Bielefeld, Germany., Förster C; Forschungsverbund BioMedizin Bielefeld/OWL FBMB e. V., Maraweg 21, 33617 Bielefeld, Germany.; Institute of Pathology, KRH Hospital Nordstadt, Haltenhoffstrasse 41, Affiliated with the Protestant Hospital of Bethel Foundation, 30167 Hannover, Germany., Wilkens L; Forschungsverbund BioMedizin Bielefeld/OWL FBMB e. V., Maraweg 21, 33617 Bielefeld, Germany.; Institute of Pathology, KRH Hospital Nordstadt, Haltenhoffstrasse 41, Affiliated with the Protestant Hospital of Bethel Foundation, 30167 Hannover, Germany., Greiner JFW; Department of Cell Biology, University of Bielefeld, Universitätsstrasse 25, 33615 Bielefeld, Germany.; Forschungsverbund BioMedizin Bielefeld/OWL FBMB e. V., Maraweg 21, 33617 Bielefeld, Germany., Kaltschmidt C; Department of Cell Biology, University of Bielefeld, Universitätsstrasse 25, 33615 Bielefeld, Germany.; Forschungsverbund BioMedizin Bielefeld/OWL FBMB e. V., Maraweg 21, 33617 Bielefeld, Germany., Kaltschmidt B; Department of Cell Biology, University of Bielefeld, Universitätsstrasse 25, 33615 Bielefeld, Germany.; Forschungsverbund BioMedizin Bielefeld/OWL FBMB e. V., Maraweg 21, 33617 Bielefeld, Germany.; Molecular Neurobiology, Bielefeld University, Universitätsstrasse 25, 33615 Bielefeld, Germany. |
| Abstrakt: |
There is growing evidence that cancer stem cells (CSCs), a small subpopulation of self-renewal cancer cells, are responsible for tumor growth, treatment resistance, and cancer relapse and are thus of enormous clinical interest. Here, we aimed to isolate new CSC-like cells derived from human primary non-small cell lung cancer (NSCLC) specimens and to analyze the influence of different inhibitors of NF-κB and MYC signaling on cell survival. CSC-like cells were established from three squamous cell carcinomas (SCC) and three adenocarcinomas (AC) of the lung and were shown to express common CSC markers such as Prominin-1, CD44-antigen, and Nestin. Further, cells gave rise to spherical cancer organoids. Inhibition of MYC and NF-κB signaling using KJ-Pyr-9, dexamethasone, and pyrrolidinedithiocarbamate resulted in significant reductions in cell survival for SCC- and AC-derived cells. However, inhibition of the protein-protein interaction of MYC/NMYC proto-oncogenes with Myc-associated factor X (MAX) using KJ-Pyr-9 revealed the most promising survival-decreasing effects. Next to the establishment of six novel in vitro models for studying NSCLC-derived CSC-like populations, the presented investigations might provide new insights into potential novel therapies targeting NF-κB/MYC to improve clinical outcomes in NSCLC patients. Nevertheless, the full picture of downstream signaling still remains elusive. |
