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      Utilization of lung cancer cell lines for the study of lung cancer stem cells

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          Abstract

          Lung cancer is one of the most l ethal types of cancer, and its poor prognosis is primarily due to drug resistance and cancer recurrence. As it is associated with a low five-year survival rate, lung cancer stem cells (LCSCs) have been the subject of numerous recent studies. For these studies of LCSCs, lung cancer cell lines are more commonly used than lung cancer tissues obtained from patients, as they are easier to acquire. The methods utilized for the identification of LCSCs from lung cancer cell lines include fluorescence activated cell sorting (FACS), magnetic activated cell sorting (MACS), sphere-forming assay and bacterial surface display library screening. As LCSCs have certain proteins expressed on the surface (CD133, CD44 and CD24) or in the cytoplasm (ALDH and ABCG2), which may act as specific markers, the most frequently used technique to identify and obtain LCSCs is FACS. The current lack of recognized biomarkers in LCSCs makes the identification of LCSCs problematic. Furthermore, the various proportions of LCSCs in specific cell lines, as revealed by numerous previous studies, may cause the LCSC model to be questioned with regard to whether the utilization of certain lung cancer cell lines is dependable for LCSC studies. The current review focuses on lung cancer cell lines that are used for the study of LCSCs and the methods available to identify LCSCs with various markers. The present study also aimed to determine the proportion of LCSCs present in specific cell lines reported by various studies, and to discuss the suitability of specific lung cancer cell lines for the study of LCSCs.

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          Highly tumorigenic lung cancer CD133+ cells display stem-like features and are spared by cisplatin treatment.

          The identification of lung tumor-initiating cells and associated markers may be useful for optimization of therapeutic approaches and for predictive and prognostic information in lung cancer patients. CD133, a surface glycoprotein linked to organ-specific stem cells, was described as a marker of cancer-initiating cells in different tumor types. Here, we report that a CD133+, epithelial-specific antigen-positive (CD133+ESA+) population is increased in primary nonsmall cell lung cancer (NSCLC) compared with normal lung tissue and has higher tumorigenic potential in SCID mice and expression of genes involved in stemness, adhesion, motility, and drug efflux than the CD133(-) counterpart. Cisplatin treatment of lung cancer cells in vitro resulted in enrichment of CD133+ fraction both after acute cytotoxic exposure and in cells with stable cisplatin-resistant phenotype. Subpopulations of CD133+ABCG2+ and CD133+CXCR4+ cells were spared by in vivo cisplatin treatment of lung tumor xenografts established from primary tumors. A tendency toward shorter progression-free survival was observed in CD133+ NSCLC patients treated with platinum-containing regimens. Our results indicate that chemoresistant populations with highly tumorigenic and stem-like features are present in lung tumors. The molecular features of these cells may provide the rationale for more specific therapeutic targeting and the definition of predictive factors in clinical management of this lethal disease.
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            Aldehyde dehydrogenase 1 is a tumor stem cell-associated marker in lung cancer.

            Tumor contains small population of cancer stem cells (CSC) that are responsible for its maintenance and relapse. Analysis of these CSCs may lead to effective prognostic and therapeutic strategies for the treatment of cancer patients. We report here the identification of CSCs from human lung cancer cells using Aldefluor assay followed by fluorescence-activated cell sorting analysis. Isolated cancer cells with relatively high aldehyde dehydrogenase 1 (ALDH1) activity display in vitro features of CSCs, including capacities for proliferation, self-renewal, and differentiation, resistance to chemotherapy, and expressing CSC surface marker CD133. In vivo experiments show that the ALDH1-positive cells could generate tumors that recapitulate the heterogeneity of the parental cancer cells. Immunohistochemical analysis of 303 clinical specimens from three independent cohorts of lung cancer patients and controls show that expression of ALDH1 is positively correlated with the stage and grade of lung tumors and related to a poor prognosis for the patients with early-stage lung cancer. ALDH1 is therefore a lung tumor stem cell-associated marker. These findings offer an important new tool for the study of lung CSCs and provide a potential prognostic factor and therapeutic target for treatment of the patients with lung cancer.
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              Cancer stem cell definitions and terminology: the devil is in the details.

              The cancer stem cell (CSC) concept has important therapeutic implications, but its investigation has been hampered both by a lack of consistency in the terms used for these cells and by how they are defined. Evidence of their heterogeneous origins, frequencies and their genomic, as well as their phenotypic and functional, properties has added to the confusion and has fuelled new ideas and controversies. Participants in The Year 2011 Working Conference on CSCs met to review these issues and to propose a conceptual and practical framework for CSC terminology. More precise reporting of the parameters that are used to identify CSCs and to attribute responses to them is also recommended as key to accelerating an understanding of their biology and developing more effective methods for their eradication in patients.
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                Author and article information

                Journal
                Oncol Lett
                Oncol Lett
                OL
                Oncology Letters
                D.A. Spandidos
                1792-1074
                1792-1082
                May 2018
                14 March 2018
                14 March 2018
                : 15
                : 5
                : 6791-6798
                Affiliations
                [1 ]Department of Medical Oncology, Cancer Center, Lung Cancer Center and State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, P.R. China
                [2 ]Department of Oncology, The Second People's Hospital of Neijiang, Neijiang, Sichuan 641000, P.R. China
                Author notes
                Correspondence to: Dr Feng Luo, Department of Medical Oncology, Cancer Center, Lung Cancer Center and State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, 37 GuoXue Lane, Chengdu, Sichuan 610041, P.R. China, E-mail: luofeng@ 123456medmail.com.cn
                [*]

                Contributed equally

                Article
                OL-0-0-8265
                10.3892/ol.2018.8265
                5920960
                29731860
                001cedf7-b178-408c-875c-b991c865fdb9
                Copyright: © Wang et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

                History
                : 29 July 2015
                : 30 March 2017
                Categories
                Review

                Oncology & Radiotherapy
                lung cancer,cancer cell line,cancer stem cell,marker,proportion
                Oncology & Radiotherapy
                lung cancer, cancer cell line, cancer stem cell, marker, proportion

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