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Establishment and Characterization of CD133+/ABCG2+ Multi-drug Resistant Lung Carcinoma Cells Subpopulation


Zhao Yarui1, Zhang Lifan2*, Liu Te3
1Shanghai Pharmaceutical Vocational College, Shanghai 200050, China; 2Huadong Hospital Affiliated to Fudan University, Shanghai 200040, China; 3Shanghai Geriatric Institute of Chinese Medicine, Shanghai 200031, China
Abstract: Multi-drug resistance is an important element which leads to ineffectiveness of chemotherapeutics. Identification of subpopulations of cancerous lung cells with multi-drug resistance and cancer stem cell properties has recently become a major research interest. We identified a subpopulation from the primary lung tumor tissues, which had high surface expression of both CD133 and ABCG2. We found this subpopulation of cells termed CD133+/ABCG2+ also overexpressed stem cells markers such as Nanog, Oct4, Sox2, Nestin, CD44, CD117, CD133 and ABCG2. These cells are not only highly prolific and invasive, but also resistant to treatment with a variety of chemotherapeutics such as casplatin and gemcitabine. Additionally, CD133+/ABCG2+ cells can readily form tumors in vivo in a relatively short time. To investigate the mechanism of aggressive tumor growth and drug resistance, we examined the CpG islands on the ABCG2 promoter of CD133+/ABCG2+ cells and found they were remarkably hypomethylated. Thus, these data suggest that CD133+/ABCG2+ cells could be reliably sorted from the human lung cancer primary tissues, and represent a valuable model for studying cancer cell physiology and multi-drug resistance. Furthermore, identification and study of these cells could have a profound impact on selection of individual treatment strategies, clinical outcome, and the design or selection of the next generation of chemotherapeutic agents.


CSTR: 32200.14.cjcb.2013.10.0004