title: Cell-based selection provides novel molecular probes for cancer stem cells.
abstract: Cancer stem cells (CSC) represent a malignant subpopulation of cells in hierarchically organized tumors. They constitute a subpopulation of malignant cells within a tumor mass and possess the ability to self-renew giving rise to heterogeneous tumor cell populations with a complex set of differentiated tumor cells. CSC may be the cause of metastasis and therapeutic refractory disease. Because few markers exist to identify and isolate pure CSC, we used cell-based Systematic Evolution of Ligands by EXponential enrichment (cell-SELEX) to create DNA aptamers that can identify novel molecular targets on the surfaces of live CSC. Out of 22 putative DNA sequences, 3 bound to ~90% and 5 bound to ~15% of DU145 prostate cancer cells. The 15% of cells that were positive for the second panel of aptamers expressed high levels of E-cadherin and CD44, had high aldehyde dehydrogenase 1 activity, grew as spheroids under nonadherent culture conditions, and initiated tumors in immune-compromised mice. The discovery of the molecular targets of these aptamers could reveal novel CSC biomarkers.
authors.affiliation: Department of Chemistry, University of Florida, Gainesville, FL, USA.
authors.forename: Kwame
authors.initials: K
authors.lastname: Sefah
authors.forename: Kyung-Mi
authors.initials: KM
authors.lastname: Bae
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Phillips
authors.forename: Dietmar W
authors.initials: DW
authors.lastname: Siemann
authors.forename: Zhen
authors.initials: Z
authors.lastname: Su
authors.forename: Steve
authors.initials: S
authors.lastname: McClellan
authors.forename: Johannes
authors.initials: J
authors.lastname: Vieweg
authors.forename: Weihong
authors.initials: W
authors.lastname: Tan
mesh_terms: D000818:Animals; D052157:Aptamers, Nucleotide; D014408:Biomarkers, Tumor / Q000378:metabolism*; D005434:Flow Cytometry; D006801:Humans; D007091:Image Processing, Computer-Assisted; D016130:Immunophenotyping; D008297:Male; D051379:Mice; D015335:Molecular Probes; D014411:Neoplastic Stem Cells / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000378:metabolism*; D052156:SELEX Aptamer Technique; D018874:Spheroids, Cellular; D014407:Tumor Cells, Cultured
chemical_list: D052157:Aptamers, Nucleotide; D014408:Biomarkers, Tumor; D015335:Molecular Probes