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

Clement, Virginie; Marino, Denis; Burkhardt, Karim; Teta, Patrick; Leyvraz, Fabienne; Schatlo, Bawarjan; Frank, Stephan; Schaller, Karl Lothard; Castella, Vincent; Radovanovic, Ivan

doi:10.1093/neuonc/nos084

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Title		Quantification, self-renewal, and genetic tracing of FL1⁺ tumor-initiating cells in a large cohort of human gliomas
Authors		Clement, Virginie Marino, Denis Burkhardt, Karim Teta, Patrick Leyvraz, Fabienne Schatlo, Bawarjan Frank, Stephan Schaller, Karl Lothard Castella, Vincent Radovanovic, Ivan show all authors [1 - 10]
Published in		Neuro-oncology. 2012, vol. 14, no. 6, p. 720-35
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
Identifiers		DOI: 10.1093/neuonc/nos084 PMID: 22584872
Full text		Article (Published version) (481 Kb) - Limited access to UNIGE
Structures		Faculté de médecine / Section de médecine fondamentale / Département de pathologie et immunologie Faculté de médecine / Section de médecine clinique / Département des neurosciences cliniques Faculté de médecine / Section de médecine fondamentale / Département de neurosciences fondamentales
Research groups		Groupe Schaller Karl Lothard (neurochirurgie) (851) Métastases du foie (657)
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. 720-35. doi: 10.1093/neuonc/nos084 https://archive-ouverte.unige.ch/unige:28691