Page 40 - Read Online

Rath et al. J Cancer Metastasis Treat 2020;6:30 Journal of Cancer
DOI: 10.20517/2394-4722.2020.51 Metastasis and Treatment

Original Article Open Access

Protection of small-cell lung cancer circulating
tumor cells by cellular fragmentation

Barbara Rath , Adelina Plangger , Doris Moser , Maximilian Hochmair , Ernst Ulsperger , Gerhard
3
2
4
1
1
Hamilton 1
1 Department of Vascular Surgery, Medical University of Vienna, Vienna A-1190, Austria.
2 Department of Cranio-Maxillofacial and Oral Surgery, Medical University of Vienna, Vienna A-1090, Austria.
3 Hospital Floridsdorf, Vienna A-1210, Austria.
4 Hospital Horn, Horn A-3580, Austria.
Correspondence to: Dr. Gerhard Hamilton, Department of Vascular Surgery, Medical University of Vienna, Spitalgasse 23,
Austria A-1090. E-mail: gerhard.hamilton@meduniwien.ac.at
How to cite this article: Rath B, Plangger A, Moser D, Hochmair M, Ulsperger E, Hamilton G. Protection of small-cell lung cancer
circulating tumor cells by cellular fragmentation. J Cancer Metastasis Treat 2020;6:30.
http://dx.doi.org/10.20517/2394-4722.2020.51
Received: 25 May 2020 First Decision: 14 Jul 2020 Revised: 17 Jul 2020 Accepted: 22 Jul 2020 Published: 17 Sep 2020

Academic Editor: Wei Zhang Copy Editor: Cai-Hong Wang Production Editor: Jing Yu

Abstract
Aim: Small-cell lung cancer (SCLC) disseminates aggressively and may exhibit high chemoresistance and poor
survival rates. In this study, we aimed to investigate a new mechanism of drug resistance for SCLC circulating
tumor cells (CTCs).

Methods: SCLC CTC cell lines (n = 4) which shed cellular fragments (MAT), as demonstrated by light and scanning
electron microscopy, are compared to permanent SCLC lines. Selected proteins are detected by proteome arrays
and the functional impact of MAT is studied using cytotoxicity tests involving cisplatin and Topotecan.

Results: The SCLC CTC lines revealed layers of attached cellular fragments with a range of decreasing sizes
from intact cells (approximately 12 µm) down to small debris (approximately 2 µm) which are not detectable in
permanent SCLC lines. Intact SCLC CTC clusters represent cores of these fragment-coated spheroids. Proteome
profiling of MAT revealed a protein pattern similar to intact cells. Chemosensitivity tests employing SCLC and
SCLC CTC lines with chemotherapeutics used in therapy of SCLC demonstrated an inhibitory activity of MAT on
the resulting cytotoxicity.

Conclusion: Generation of cell-associated debris by SCLC CTCs offers protective effects against cytotoxic drugs,
representing a novel mechanism allowing survival of SCLC CTCs in patients.

© The Author(s) 2020. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use,
sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long
as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license,
and indicate if changes were made.

www.jcmtjournal.com