title: Aldehyde dehydrogenase-1 is a specific marker for stem cells in human lung adenocarcinoma.
abstract: To investigate whether aldehyde dehydrogenase-1 (ALDH-1) in human lung cancer can be used as a sorting marker for stem cells in targeted therapies against human lung cancer. Spheres were induced by incubating cancer cells in a serum-free medium and formed with epidermal growth factor and fibroblast growth factor-10 (FGF10). Spheroid cells were combined with flow cytometry using the Aldefluor reagent to separate the SSCloALDEbr (ALDH-1-positive) cells. Cancer stem cells (CSCs) were characterized by their proliferation, colony formation, and tumorigenesis in nude mice and using phenotypic analysis. Float-growing spheres ("pulmospheres") were developed after SPC-A1 cells were cultured in a serum-free medium. The resultant sphere-forming cells included ALDH-1-positive cells as high as 15.13%. ALDH-1-positive CSCs have high proliferative ability, high cloning efficiency, and strong tumorigenicity. The rate of SSC(lo)ALDE(br) cell colony formation was 1.3-5.6%, whereas that of ALDE(-) cell colony formation was only 0-1.2% (P < 0.05). A cell count of only 1 × 10(3) SSC(lo)ALDE(br) cells was necessary to form tumors, whereas at least l × 10(5) ALDE(-) cells formed tumors. The same number of SSC(lo)ALDE(br) cells also formed larger tumors in a short latency period of tumor formation. The expression rates of CD133 in the SSC(lo)ALDE(br) and ALDE(-) cells were 16.31% (16.31 × 10(4)/10(6)) and 2.56% (2.56 × 10(4)/10(6)), respectively (P < 0.01). Moreover, the expression rates of ABCG2 in SSC(lo)ALDE(br) and ALDE(-) cells were 17.62% (17.62 × 10(4)/10(6)) and 3.45% (3.45 × 10(4)/10(6)), respectively (P < 0.01). Human lung adenocarcinoma bears CSCs, and ALDH-1 can act as a specific marker for human lung CSCs.
authors.affiliation: Department of Respiratory Medicine, The First Affiliated Hospital of Harbin Medical University, 23Youzheng Street, Nangang District, 150001 Harbin City, Heilongjiang, China. liangdong-1224@163.com
authors.forename: Dong
authors.initials: D
authors.lastname: Liang
authors.forename: Yuzhi
authors.initials: Y
authors.lastname: Shi
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology / Q000473:pathology*; D000080924:Aldehyde Dehydrogenase 1 Family; D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism*; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000378:metabolism / Q000473:pathology*; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D005434:Flow Cytometry; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism*; D008175:Lung Neoplasms / Q000201:enzymology / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D014411:Neoplastic Stem Cells / Q000201:enzymology* / Q000473:pathology; D010641:Phenotype; D050697:Retinal Dehydrogenase / Q000378:metabolism*; D018874:Spheroids, Cellular / Q000201:enzymology* / Q000473:pathology; D014410:Tumor Stem Cell Assay
chemical_list: D014408:Biomarkers, Tumor; D016895:Culture Media, Serum-Free; D007527:Isoenzymes; D000080924:Aldehyde Dehydrogenase 1 Family; C510223:ALDH1A1 protein, human; C515028:ALDH1A1 protein, mouse; D050697:Retinal Dehydrogenase