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Quantification, self-renewal, and genetic tracing of FL1⁺ tumor-initiating cells in a large cohort of human gliomas |
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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 | PMID: 22584872 | |
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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 |