title: Complex display of putative tumor stem cell markers in the NCI60 tumor cell line panel.
abstract: Tumor stem cells or cancer initiating cells (CICs) are single tumor cells that can regenerate a tumor or a metastasis. The identification and isolation of CICs remain challenging, and a variety of putative CIC markers have been described. We hypothesized that cell lines of the NCI60 panel contain CICs and express putative CIC markers. We investigated expression of putative CIC surface markers (CD15, CD24, CD44, CD133, CD166, CD326, PgP) and the activity of aldehyde dehydrogenase in the NCI60 panel singly and in combination by six-color fluorescence-activated cell sorting analysis. All investigated markers were expressed in cell lines of the NCI60 panel. Expression levels of individual markers varied widely across the 60 cell lines, and neither single marker expression nor simple combinations nor co-expression patterns correlated with the colony-formation capacity of cell lines. Rather, marker expression patterns correlated with tumor types in multidimensional analysis. Whereas some expression patterns correlated with tumor entities such as basal breast cancer, other expression patterns occurred across different tumor types and largely related to expression of a more mesenchymal phenotype in individual breast, lung, renal, and melanoma cell lines. Our data for the first time demonstrate that tumor cell lines display CIC markers in a complex pattern that relates to the tumor type. The complexity and tumor type specificity of marker display creates challenges for the application of cell sorting and other approaches to isolation of putative tumor stem cell populations and suggests that therapeutic targeting strategies will need to take this into account.
authors.affiliation: Cell and Cancer Biology Branch, National Cancer Institute, Bethesda, Maryland 20892, USA. chrisstu@mail.nih.gov
authors.forename: Christina H
authors.initials: CH
authors.lastname: Stuelten
authors.forename: Susan D
authors.initials: SD
authors.lastname: Mertins
authors.forename: Johanna I
authors.initials: JI
authors.lastname: Busch
authors.forename: Meghan
authors.initials: M
authors.lastname: Gowens
authors.forename: Dominic A
authors.initials: DA
authors.lastname: Scudiero
authors.forename: Mark W
authors.initials: MW
authors.lastname: Burkett
authors.forename: Karen M
authors.initials: KM
authors.lastname: Hite
authors.forename: Mike
authors.initials: M
authors.lastname: Alley
authors.forename: Melinda
authors.initials: M
authors.lastname: Hollingshead
authors.forename: Robert H
authors.initials: RH
authors.lastname: Shoemaker
authors.forename: John E
authors.initials: JE
authors.lastname: Niederhuber
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D020869:Gene Expression Profiling; D006801:Humans; D014411:Neoplastic Stem Cells / Q000166:cytology / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor