Identification and characterization of cells with cancer stem cell properties in human primary lung cancer cell lines
Authors: Liwei Ma
Ping Wang
Else Munthe
Mengyu Wang
Nomdo Anton Christiaan Westerdaal
Zhenhe Suo
Gunnar Kvalheim
Gustav Gaudernack
Steinar Solberg
Quanli Gao
Journal: PloS one (2013)
Discipline: Multidisciplinary
Keywords: Lung cancer; therapy resistance; cancer stem cells; primary lung cancer cell lines; subtypes
Affiliations: Department of Immunology, Institute for Cancer Research, Oslo University Hospital, Radiumhospitalet, Oslo, Norway.

Abstract:  Lung cancer (LC) with its different subtypes is generally known as a therapy resistant cancer with the highest morbidity rate worldwide. Therapy resistance of a tumor is thought to be related to cancer stem cells (CSCs) within the tumors. There have been indications that the lung cancer is propagated and maintained by a small population of CSCs. To study this question we established a panel of 15 primary lung cancer cell lines (PLCCLs) from 20 fresh primary tumors using a robust serum-free culture system. We subsequently focused on identification of lung CSCs by studying these cell lines derived from 4 representative lung cancer subtypes such as small cell lung cancer (SCLC), large cell carcinoma (LCC), squamous cell carcinoma (SCC) and adenocarcinoma (AC). We identified a small population of cells strongly positive for CD44 (CD44(high)) and a main population which was either weakly positive or negative for CD44 (CD44(low/-)). Co-expression of CD90 further narrowed down the putative stem cell population in PLCCLs from SCLC and LCC as spheroid-forming cells were mainly found within the CD44(high)CD90(+) sub-population. Moreover, these CD44(high)CD90(+) cells revealed mesenchymal morphology, increased expression of mesenchymal markers N-Cadherin and Vimentin, increased mRNA levels of the embryonic stem cell related genes Nanog and Oct4 and increased resistance to irradiation compared to other sub-populations studied, suggesting the CD44(high)CD90(+) population a good candidate for the lung CSCs. Both CD44(high)CD90(+) and CD44(high)CD90(-) cells in the PLCCL derived from SCC formed spheroids, whereas the CD44(low/-) cells were lacking this potential. These results indicate that CD44(high)CD90(+) sub-population may represent CSCs in SCLC and LCC, whereas in SCC lung cancer subtype, CSC potentials were found within the CD44(high) sub-population. 

Retracted: Yes

PubPeer comments:
 Most of the dots are identical and the difference in CD44 expression is marginal. ![file] ![file] ![file] , 
 This article was retracted https: journals.plos.org plosone article?id=10.1371 journal.pone.0232726  Following the publication of this article [1], concerns were raised regarding the flow cytometry data reported in Fig 3: There are similarities in dot plot patterns between the right panel of Fig 3A and the right panel of Fig 3C. Although the plots are not exact duplicates, the similarities observed are not expected from plots derived from distinct datasets. The original data underlying Fig 3 are no longer available and thus it is not possible to resolve the concerns pertaining to the reliability of the integrity of the published figure. The Commission on Research Integrity at Oslo University Hospital and Institute of Clinical Medicine, University of Oslo has completed an investigation and concluded that there was evidence of scientific misconduct. In light of the outstanding concerns with panels in Fig 3 that question the integrity of these data and the outcome of an internal institutional investigation, the PLOS ONE Editors retract this article. PW, QG, ZS, EM, LM, and GG did not agree with the retraction. SS, MW, NACW, and GK did not respond to the retraction decision. ,