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 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.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2021 |
|---|---|
| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:10 |
|---|---|
| Enthalten in: |
Cells - 10(2021), 5 vom: 27. Apr. |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Windmöller, Beatrice A [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Adenocarcinoma |
|---|
| Anmerkungen: |
Date Completed 22.10.2021 Date Revised 22.10.2021 published: Electronic Citation Status MEDLINE |
|---|
| doi: |
10.3390/cells10051024 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM324785461 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM324785461 | ||
| 003 | DE-627 | ||
| 005 | 20231225191044.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2021 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.3390/cells10051024 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1082.xml |
| 035 | |a (DE-627)NLM324785461 | ||
| 035 | |a (NLM)33925297 | ||
| 035 | |a (PII)1024 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Windmöller, Beatrice A |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Novel Primary Human Cancer Stem-Like Cell Populations from Non-Small Cell Lung Cancer |b Inhibition of Cell Survival by Targeting NF-κB and MYC Signaling |
| 264 | 1 | |c 2021 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 22.10.2021 | ||
| 500 | |a Date Revised 22.10.2021 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a MYC | |
| 650 | 4 | |a NF-κB | |
| 650 | 4 | |a NSCLC | |
| 650 | 4 | |a adenocarcinoma | |
| 650 | 4 | |a cancer stem cell-like cells | |
| 650 | 4 | |a squamous cell carcinoma | |
| 650 | 7 | |a NF-kappa B |2 NLM | |
| 650 | 7 | |a Proto-Oncogene Proteins c-myc |2 NLM | |
| 650 | 7 | |a Tumor Necrosis Factor-alpha |2 NLM | |
| 700 | 1 | |a Beshay, Morris |e verfasserin |4 aut | |
| 700 | 1 | |a Helweg, Laureen P |e verfasserin |4 aut | |
| 700 | 1 | |a Flottmann, Clara |e verfasserin |4 aut | |
| 700 | 1 | |a Beermann, Miriam |e verfasserin |4 aut | |
| 700 | 1 | |a Förster, Christine |e verfasserin |4 aut | |
| 700 | 1 | |a Wilkens, Ludwig |e verfasserin |4 aut | |
| 700 | 1 | |a Greiner, Johannes F W |e verfasserin |4 aut | |
| 700 | 1 | |a Kaltschmidt, Christian |e verfasserin |4 aut | |
| 700 | 1 | |a Kaltschmidt, Barbara |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Cells |d 2011 |g 10(2021), 5 vom: 27. Apr. |w (DE-627)NLM227066421 |x 2073-4409 |7 nnns |
| 773 | 1 | 8 | |g volume:10 |g year:2021 |g number:5 |g day:27 |g month:04 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.3390/cells10051024 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 10 |j 2021 |e 5 |b 27 |c 04 | ||