Novel Primary Human Cancer Stem-Like Cell Populations from Non-Small Cell Lung Cancer: Inhibition of Cell Survival by Targeting NF-κB and MYC Signaling

• Published in: Cells (Basel, Switzerland) Switzerland), 2021-04, Vol.10 (5), p.1024
• Main Authors: Windmöller, Beatrice A, Beshay, Morris, Helweg, Laureen P, Flottmann, Clara, Beermann, Miriam, Förster, Christine, Wilkens, Ludwig, Greiner, Johannes F W, Kaltschmidt, Christian, Kaltschmidt, Barbara
• Format: Article
• Language: English
• Subjects: adenocarcinoma; cancer stem cell-like cells; CD44 antigen; Cell self-renewal; Cell survival; Coagulation factors; Dexamethasone; Growth factors; Lung cancer; Medical prognosis; Metastasis; MYC; Myc protein; Nestin; NF-κB; NF-κB protein; Non-small cell lung carcinoma; NSCLC; Organoids; Penicillin; Population; Proto-oncogenes; Small cell lung carcinoma; Spheres; Squamous cell carcinoma; Stem cells; Transcription factors
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells10051024

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.