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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

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...

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Autores principales: Windmöller, Beatrice A., Beshay, Morris, Helweg, Laureen P., Flottmann, Clara, Beermann, Miriam, Förster, Christine, Wilkens, Ludwig, Greiner, Johannes F. W., Kaltschmidt, Christian, Kaltschmidt, Barbara
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8145874/
https://www.ncbi.nlm.nih.gov/pubmed/33925297
http://dx.doi.org/10.3390/cells10051024
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author Windmöller, Beatrice A.
Beshay, Morris
Helweg, Laureen P.
Flottmann, Clara
Beermann, Miriam
Förster, Christine
Wilkens, Ludwig
Greiner, Johannes F. W.
Kaltschmidt, Christian
Kaltschmidt, Barbara
author_facet Windmöller, Beatrice A.
Beshay, Morris
Helweg, Laureen P.
Flottmann, Clara
Beermann, Miriam
Förster, Christine
Wilkens, Ludwig
Greiner, Johannes F. W.
Kaltschmidt, Christian
Kaltschmidt, Barbara
author_sort Windmöller, Beatrice A.
collection PubMed
description 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.
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spelling pubmed-81458742021-05-26 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 Windmöller, Beatrice A. Beshay, Morris Helweg, Laureen P. Flottmann, Clara Beermann, Miriam Förster, Christine Wilkens, Ludwig Greiner, Johannes F. W. Kaltschmidt, Christian Kaltschmidt, Barbara Cells Article 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. MDPI 2021-04-27 /pmc/articles/PMC8145874/ /pubmed/33925297 http://dx.doi.org/10.3390/cells10051024 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Windmöller, Beatrice A.
Beshay, Morris
Helweg, Laureen P.
Flottmann, Clara
Beermann, Miriam
Förster, Christine
Wilkens, Ludwig
Greiner, Johannes F. W.
Kaltschmidt, Christian
Kaltschmidt, Barbara
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
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8145874/
https://www.ncbi.nlm.nih.gov/pubmed/33925297
http://dx.doi.org/10.3390/cells10051024
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