title: Persistence of CD133+ cells in human and mouse glioma cell lines: detailed characterization of GL261 glioma cells with cancer stem cell-like properties.
abstract: The concept of cancer stem cells suggests that there are malignant stem-like cells within a tumor that are responsible for tumor renewal and resistance to cytotoxic therapies. Studies have identified glioma stem-like cells that extrude Hoechst 33342 dye, representing a double-negative "side population" (SP) thought to be selectively resistant to drug therapy. A CD133+ stem cell-like subpopulation has been isolated from a human glioma that was enriched for tumor-initiating cells. It is unknown whether CD133+ cells with similar phenotype persist in established glioma cell lines, or if CD133 is a marker of glioma stem-like cells in rodents. We investigated whether CD133+ and SP cells existed in the GL261 cell line, a syngeneic mouse glioma model that is widely used for preclinical and translational research. Intracerebral injection of less than 100 CD133+ GL261 cells formed tumors, whereas it required 10,000 CD133(-) cells to initiate a tumor. CD133+ GL261 cells expressed nestin, formed tumor spheres with high frequency, and differentiated into glial and neuronal-like cells. Similar to GL261, seven human glioma cell lines analyzed also contained a rare CD133+ population. Surprisingly, we found that CD133+ GL261 cells did not reside in the SP, nor did the majority ( approximately 94%) of CD133+ human glioma cells. These results demonstrate that the expression of CD133 in murine glioma cells is associated with enhanced tumorigenicity and a stem-like phenotype. This study also reveals a previously unrecognized level of heterogeneity in glioma cell lines, exposing several populations of cells that have characteristics of cancer stem cells.
authors.affiliation: Department of Neurosurgery, University of Minnesota Medical School, Minneapolis, MN 55455, USA.
authors.forename: Anhua
authors.initials: A
authors.lastname: Wu
authors.forename: Seunguk
authors.initials: S
authors.lastname: Oh
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Wiesner
authors.forename: Katya
authors.initials: K
authors.lastname: Ericson
authors.forename: Lisa
authors.initials: L
authors.lastname: Chen
authors.forename: Walter A
authors.initials: WA
authors.lastname: Hall
authors.forename: Paul E
authors.initials: PE
authors.lastname: Champoux
authors.forename: Walter C
authors.initials: WC
authors.lastname: Low
authors.forename: John R
authors.initials: JR
authors.lastname: Ohlfest
mesh_terms: D000071916:AC133 Antigen; D000818:Animals; D015703:Antigens, CD; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D005910:Glioma / Q000473:pathology*; D006023:Glycoproteins; D006801:Humans; D051379:Mice; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000473:pathology*; D009457:Neuroglia; D009474:Neurons; D010455:Peptides
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; C000606024:Prom1 protein, mouse