title: Pivotal role of CD38 biomarker in combination with CD24, EpCAM, and ALDH for identification of H460 derived lung cancer stem cells.
abstract: Lung cancer is the number one killer among all cancers and is estimated to kill over 170,000 individual in 2010 in the United States. However, little is understood about the role of tumor initiating cells in the lung cancer and whether these cells play a major role in initiation, drug resistance, and metastases of this disease. We have isolated lungospheres from tumors grown in mice and have critically examined proposed biomarkers of lung cancer stem cells such as ALDH, EpCAM, CD133/1, CD133/2, CD24, and CD38, using global gene expression, flow cytometric analysis, and quantitative real time PCR. We present evidences that the pattern of overexpression of ALDH and EpCAM, two widely discussed biomarkers of cancer stem cells, in the tumor generated by lung cancer stem cells in mice are different that could be an indicative of tumor aggressiveness. We propose, for the first time, that CD38 in combination with CD24 is a biomarkers for H460 derived lung cancer stem cells and could be used to elucidate the characteristics of these sub-population of cells. Our results demonstrate that the combination of CD24(Low/-)/CD38+ and overexpression of ALDH1 and EpCAM is the signature of enriched tumor initiating cells in H460 non-small cell lung cancer cell line. Our results propose H460-derived cancer stem cells as a well defined cell for future comprehensive analysis of putative lung cancer stem cells-like cells.
authors.affiliation: NovaRx Corporation, Cancer Stem Cell Department, 6828 Nancy Ridge Drive, San Diego 92121, USA. fkarimi@novarx.com
authors.forename: Feridoun
authors.initials: F
authors.lastname: Karimi-Busheri
authors.forename: Victoria
authors.initials: V
authors.lastname: Zadorozhny
authors.forename: Tony
authors.initials: T
authors.lastname: Li
authors.forename: Helen
authors.initials: H
authors.lastname: Lin
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Shawler
authors.forename: Habib
authors.initials: H
authors.lastname: Fakhrai
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000235:genetics / Q000378:metabolism*; D000080924:Aldehyde Dehydrogenase 1 Family; D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D051927:CD24 Antigen / Q000235:genetics / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D000071858:Epithelial Cell Adhesion Molecule; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D020869:Gene Expression Profiling; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D008175:Lung Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D050697:Retinal Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D051927:CD24 Antigen; C497889:CD24 protein, human; D015815:Cell Adhesion Molecules; C499379:EPCAM protein, human; D000071858:Epithelial Cell Adhesion Molecule; D007527:Isoenzymes; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D000080924:Aldehyde Dehydrogenase 1 Family; C510223:ALDH1A1 protein, human; C515028:ALDH1A1 protein, mouse; D050697:Retinal Dehydrogenase; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1