en
Scientific article
English

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

Published inNeuro-oncology, vol. 14, no. 6, p. 720-735
Publication date2012
Abstract

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.

Keywords
  • 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/pathology
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Middle Aged
  • Neoplasm Grading
  • Neoplastic Stem Cells/pathology
  • Prognosis
  • Prospective Studies
  • Young Adult
Citation (ISO format)
CLEMENT, Virginie et al. Quantification, self-renewal, and genetic tracing of FL1⁺ tumor-initiating cells in a large cohort of human gliomas. In: Neuro-oncology, 2012, vol. 14, n° 6, p. 720–735. doi: 10.1093/neuonc/nos084
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Article (Published version)
accessLevelRestricted
Identifiers
ISSN of the journal1522-8517
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