title: CD15 Expression Does Not Identify a Phenotypically or Genetically Distinct Glioblastoma Population.
abstract: : Recent research has focused on the hypothesis that the growth and regeneration of glioblastoma (GB) is sustained by a subpopulation of self-renewing stem-like cells. This has led to the prediction that molecular markers for cancer stem cells in GB may provide a treatment target. One candidate marker is CD15: we wanted to determine if CD15 represented a credible stem cell marker in GB. We first demonstrated that CD15-positive (CD15+) cells were less proliferative than their CD15-negative (CD15-) counterparts in 10 patient GB tumors. Next we compared the proliferative activity of CD15+ and CD15- cells in vitro using tumor-initiating primary GB cell lines (TICs) and found no difference in proliferative behavior. Furthermore, TICs sorted for CD15+ and CD15- were not significantly different cytogenetically or in terms of gene expression profile. Sorted single CD15+ and CD15- cells were equally capable of reconstituting a heterogeneous population containing both CD15+ and CD15- cells over time, and both CD15+ and CD15- cells were able to generate tumors in vivo. No difference was found in the phenotypic or genomic behavior of CD15+ cells compared with CD15- cells from the same patient. Moreover, we found that in vitro, cells were able to interconvert between the CD15+ and CD15- states. Our data challenge the utility of CD15 as a cancer stem cell marker.
  
  
  CONCLUSIONS
  The data from this study contribute to the ongoing debate about the role of cancer stem cells in gliomagenesis. Results showed that CD15, a marker previously thought to be a cancer stem-like marker in glioblastoma, could not isolate a phenotypically or genetically distinct population. Moreover, isolated CD15-positive and -negative cells were able to generate mixed populations of glioblastoma cells in vitro.
authors.affiliation: John van Geest Centre for Brain Repair, Department of Clinical Neurosciences, Cambridge University, Cambridge, United Kingdom; MRC Cancer Unit, Hutchison/MRC Research Centre, University of Cambridge, Cambridge, United Kingdom; The Institute of Cancer Research, London, United Kingdom cw209@cam.ac.uk emmakenneyherbert@yahoo.co.uk.
authors.forename: Emma
authors.initials: E
authors.lastname: Kenney-Herbert
authors.affiliation: John van Geest Centre for Brain Repair, Department of Clinical Neurosciences, Cambridge University, Cambridge, United Kingdom; MRC Cancer Unit, Hutchison/MRC Research Centre, University of Cambridge, Cambridge, United Kingdom; The Institute of Cancer Research, London, United Kingdom.
authors.forename: Talal
authors.initials: T
authors.lastname: Al-Mayhani
authors.affiliation: John van Geest Centre for Brain Repair, Department of Clinical Neurosciences, Cambridge University, Cambridge, United Kingdom; MRC Cancer Unit, Hutchison/MRC Research Centre, University of Cambridge, Cambridge, United Kingdom; The Institute of Cancer Research, London, United Kingdom.
authors.forename: Sara G M
authors.initials: SG
authors.lastname: Piccirillo
authors.affiliation: John van Geest Centre for Brain Repair, Department of Clinical Neurosciences, Cambridge University, Cambridge, United Kingdom; MRC Cancer Unit, Hutchison/MRC Research Centre, University of Cambridge, Cambridge, United Kingdom; The Institute of Cancer Research, London, United Kingdom.
authors.forename: Joanna
authors.initials: J
authors.lastname: Fowler
authors.affiliation: John van Geest Centre for Brain Repair, Department of Clinical Neurosciences, Cambridge University, Cambridge, United Kingdom; MRC Cancer Unit, Hutchison/MRC Research Centre, University of Cambridge, Cambridge, United Kingdom; The Institute of Cancer Research, London, United Kingdom.
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Spiteri
authors.affiliation: John van Geest Centre for Brain Repair, Department of Clinical Neurosciences, Cambridge University, Cambridge, United Kingdom; MRC Cancer Unit, Hutchison/MRC Research Centre, University of Cambridge, Cambridge, United Kingdom; The Institute of Cancer Research, London, United Kingdom.
authors.forename: Philip
authors.initials: P
authors.lastname: Jones
authors.affiliation: John van Geest Centre for Brain Repair, Department of Clinical Neurosciences, Cambridge University, Cambridge, United Kingdom; MRC Cancer Unit, Hutchison/MRC Research Centre, University of Cambridge, Cambridge, United Kingdom; The Institute of Cancer Research, London, United Kingdom cw209@cam.ac.uk emmakenneyherbert@yahoo.co.uk.
authors.forename: Colin
authors.initials: C
authors.lastname: Watts
keywords: CD15; Cancer; Glioblastoma; Hierarchy; SSEA1; Stem cell