Properties of resistant cells generated from lung cancer cell lines treated with EGFR inhibitors

BMC Cancer

Research Article

Xiaojun Lian¹  Sean P Palecek¹  Gargi Ghosh²  Stephen J Kron³ 

[1] Department of Chemical and Biological Engineering, University of Wisconsin, Madison, 1415 Engineering Drive, 53706, Madison, WI, USA;Department of Chemical and Biological Engineering, University of Wisconsin, Madison, 1415 Engineering Drive, 53706, Madison, WI, USA;Department of Mechanical Engineering, University of Michigan, 48128, Dearborn, MI, USA;Ludwig Center for Metastasis Research, University of Chicago, 60637, Chicago, IL, USA;

关键词: EGFR tyrosine kinase;    Erlotinib;    Cancer stem cells;    Tumor spheroids;    Side population;   

DOI  :  10.1186/1471-2407-12-95

 received in 2011-08-03, accepted in 2012-03-20,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundEpidermal growth factor receptor (EGFR) signaling plays an important role in non-small cell lung cancer (NSCLC) and therapeutics targeted against EGFR have been effective in treating a subset of patients bearing somatic EFGR mutations. However, the cancer eventually progresses during treatment with EGFR inhibitors, even in the patients who respond to these drugs initially. Recent studies have identified that the acquisition of resistance in approximately 50% of cases is due to generation of a secondary mutation (T790M) in the EGFR kinase domain. In about 20% of the cases, resistance is associated with the amplification of MET kinase. In the remaining 30-40% of the cases, the mechanism underpinning the therapeutic resistance is unknown.MethodsAn erlotinib resistant subline (H1650-ER1) was generated upon continuous exposure of NSCLC cell line NCI-H1650 to erlotinib. Cancer stem cell like traits including expression of stem cell markers, enhanced ability to self-renew and differentiate, and increased tumorigenicity in vitro were assessed in erlotinib resistant H1650-ER1 cells.ResultsThe erlotinib resistant subline contained a population of cells with properties similar to cancer stem cells. These cells were found to be less sensitive towards erlotinib treatment as measured by cell proliferation and generation of tumor spheres in the presence of erlotinib.ConclusionsOur findings suggest that in cases of NSCLC accompanied by mutant EGFR, treatment targeting inhibition of EGFR kinase activity in differentiated cancer cells may generate a population of cancer cells with stem cell properties.

【 授权许可】

Unknown   
© Ghosh et al; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.