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Open Access 01-08-2020 | Lung Cancer | PRECLINICAL STUDIES

Effects of salinomycin and niclosamide on small cell lung cancer and small cell lung cancer circulating tumor cell lines

Authors: Maximilian Hochmair, Barbara Rath, Lukas Klameth, Ernst Ulsperger, Christoph Weinlinger, Andreas Fazekas, Adelina Plangger, Robert Zeillinger, Gerhard Hamilton

Published in: Investigational New Drugs | Issue 4/2020

Summary

Tumor dissemination and recurrence is attributed to highly resistant cancer stem cells (CSCs) which may constitute a fraction of circulating tumor cells (CTCs). Small cell lung cancer (SCLC) constitutes a suitable model to investigate the relation of CTCs and CSCs due to rapid tumor spread and a high number of CTCs. Expansion of five SCLC CTC lines (BHGc7, 10, 16, 26 and UHGc5) in vitro at our institution allowed for the analysis of CSC markers and cytotoxicity of the CSC-selective drugs salinomycin and niclosamide against CTC single cell suspensions or CTC spheroids/ tumorospheres (TOS). Salinomycin exerted dose-dependent cytotoxicity against the SCLC lines but, with exception of BHGc7 TOS, there was no markedly enhanced activity against TOS. Similarly, niclosamide exhibits high activity against BHGc7 TOS and UHGc5 TOS but not against the other CTC spheroids. High expression of the CSC marker CD133 was restricted to three SCLC tumor lines and the BHGc10 CTC line. All SCLC CTCs are CD24-positive but lack expression of CD44 and ABCG2 in contrast to the SCLC tumor lines which show a phenotype more similar to that of CSCs. The stem cell marker SOX2 was found in all CTC lines and SCLC GLC14/16, whereas elevated expression of Oct-3/4 and Nanog was restricted to BHGc26 and UHGc5. In conclusion, the SCLC CTCs established from patients with relapsed disease lack a typical CSC phenotype in respect to chemosensitivity to CSC-selective drugs, surface markers, expression of pluripotent stem cell and transcription factors.

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Title: Effects of salinomycin and niclosamide on small cell lung cancer and small cell lung cancer circulating tumor cell lines
Authors: Maximilian Hochmair
Barbara Rath
Lukas Klameth
Ernst Ulsperger
Christoph Weinlinger
Andreas Fazekas
Adelina Plangger
Robert Zeillinger
Gerhard Hamilton
Publication date: 01-08-2020
Publisher: Springer US
Keywords: Lung Cancer
Lung Cancer
SCLC
Niclosamide
Lung Cancer
SCLC
Published in: Investigational New Drugs / Issue 4/2020
Print ISSN: 0167-6997
Electronic ISSN: 1573-0646
DOI: https://doi.org/10.1007/s10637-019-00847-8

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