Quantification, self-renewal, and genetic tracing of FL1⁺ tumor-initiating cells in a large cohort of human gliomas

Neuro Oncol. 2012 Jun;14(6):720-35. doi: 10.1093/neuonc/nos084. Epub 2012 May 14.


Evidence has emerged that the initiation and growth of gliomas is sustained by a subpopulation of cancer-initiating cells (CICs). Because of the difficulty of using markers to tag CICs in gliomas, we have previously exploited more robust phenotypic characteristics, including a specific morphology and intrincic autofluorescence, to identify and isolate a subpopulation of glioma CICs, called FL1(+). The objective of this study was to further validate our method in a large cohort of human glioma and a mouse model of glioma. Seventy-four human gliomas of all grades and the GFAP-V(12)HA-ras B8 mouse model were analyzed for in vitro self-renewal capacity and their content of FL1(+). Nonneoplastic brain tissue and embryonic mouse brain were used as control. Genetic traceability along passages was assessed with microsatellite analysis. We found that FL1(+) cells from low-grade gliomas and from control nonneoplasic brain tissue show a lower level of autofluorescence and undergo a restricted number of cell divisions before dying in culture. In contrast, we found that FL1(+) cells derived from many but not all high-grade gliomas acquire high levels of autofluorescence and can be propagated in long-term cultures. Moreover, FL1(+) cells show a remarkable traceability over time in vitro and in vivo. Our results show that FL1(+) cells can be found in all specimens of a large cohort of human gliomas of different grades and in a model of genetically induced mouse glioma as well as nonneoplastic brain. However, their self-renewal capacity is variable and seems to be dependent on the tumor grade.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Retracted Publication

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Animals
  • Brain / metabolism
  • Brain Neoplasms / pathology*
  • Cell Differentiation*
  • Cell Line, Tumor
  • Cell Transformation, Neoplastic / pathology*
  • Child, Preschool
  • Disease Models, Animal
  • Female
  • Fluorescence
  • Genes, ras
  • Glial Fibrillary Acidic Protein / genetics
  • Glioma / genetics*
  • Glioma / pathology*
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Middle Aged
  • Neoplasm Grading
  • Neoplastic Stem Cells / pathology*
  • Prognosis
  • Prospective Studies
  • Young Adult


  • Glial Fibrillary Acidic Protein