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) and a main population which was either weakly positive or negative for
CD44 (CD44). 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 CD44CD90 sub-population. Moreover, these CD44CD90 cells
revealed mesenchymal morphology, increased expression of mesenchymal markers
and , increased mRNA levels of the embryonic stem cell related genes and and
increased resistance to irradiation compared to other sub-populations studied,
suggesting the CD44CD90 population a good candidate for the lung CSCs. Both
CD44CD90 and CD44CD90 cells in the PLCCL derived from SCC formed spheroids,
whereas the CD44 cells were lacking this potential. These results indicate that
CD44CD90 sub-population may represent CSCs in SCLC and LCC, whereas in SCC lung
cancer subtype, CSC potentials were found within the CD44 sub-population.
Source: Identification and characterization of cells with
cancer stem cell properties in human primary lung cancer cell lines. Wang P,
Gao Q, Suo Z, Munthe E, Solberg S, Ma L, Wang M, Westerdaal NA, Kvalheim G,
Gaudernack G (gustav.gaudernac@rr-research.no).
PLoS One. 2013;8(3):e57020.
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