Doetsch, Fiona

Fowkes, Mary

Friedel, Roland H.

Magid, Margret

Silva-Vargas, Violeta

Tejero, Rut

Tome-Garcia, Jessica

Tsankova, Nadejda

Yong, Raymund

English

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N E U RO - O N CO LO G YAbstractsSTEM-19. EGFR EXPRESSION CONFERS STEM CELL-LIKEPROPERTIES TO HUMAN NEURAL PROGENITORS ANDGLIOMASJessica Tome-Garcia1,2, Raymund Yong3, Mary Fowkes1, Margret Magid1,Rut Tejero2, Violeta Silva-Vargas5, RolandH. Friedel2, FionaDoetsch4,5, andNadejdaTsankova1,2; 1Department of Pathology, Icahn School ofMedicine atMount Sinai, New York, NY, USA; 2Department of Neuroscience andFriedman Brain Institute, Icahn School of Medicine at Mount Sinai,New York, NY, USA; 3Department of Neurosurgery, Icahn School ofMedicine at Mount Sinai, New York, NY, USA; 4Department of PathologyandCell Biology, ColumbiaUniversityMedical Center,NewYork,NY, USA;5Biozentrum, University of Basel, Basel, CH, SwitzerlandActivation of the epidermal growth factor receptor (EGFR) pathway isstrongly implicated in the proliferation and migration of neural/glial progen-itors and gliomas. EGFR is silenced after development but becomes aberrantlyoverexpressed in many low-grade and most high-grade gliomas, often in theabsence of gene-amplification/activating mutations. The phenotype andfunctional characteristics of EGFR-expressing human brain cells are notwell defined, as is the relationship of EGFR expression to gliomagenesis. Werecently reported on the selective retention of EGFR expression in adulthuman subventricular zone (SVZ) glia. Notably, we also showed a strikinglysimilar epigenetic landscape at the wild-type EGFR promoter between germi-nalmatrix/SVZ andEGFR-expressing gliomas.Hereweundertook a detailedcharacterization of EGFR-expressing cells in the developing and adult humanbrain using warm postmortem material, and in human glioblastomas afterfresh resection, hypothesizing that EGFR-positive cells harbor stem cell-likeproperties invitro,whichmay implicate them ingliomagenesis.Tobetter char-acterize the phenotype of human EGFR-expressing brain cells in vivo, we per-formeddetailed confocal immunofluorescenceanalysiswithmarkers for glial/neuronal lineage differentiation and proliferation. We found that duringneural development, many EGFR-positive cells co-express markers of oligo-dendrocyte lineage, such as Olig2, similarly to most glioblastomas. We thenanalyzed the behavior of these cells in vitro.We used our novel, human-basedprotocol to isolate cells directly from fresh human samples, taking advantageof the inherent binding affinity of EGFR for its natural ligand, EGF.Intriguingly, we found that EGFR-positive, but not EGFR-negative, cells iso-lated from germinal matrix and from glioblastomas display stem-cell charac-teristics in culture, including self-renewal and trilineage differentiation. Ourfindings suggest that EGFR expression confers stem-cell-like properties tohuman progenitors and glioma cells, hint that its maintenance may play arole in gliomagenesis, and provide a novel isolation platform of functionallydefined EGFR+ glioma populations for further molecular analyses.Neuro-Oncology 17:v208–v213, 2015.doi:10.1093/neuonc/nov234.19Published by Oxford University Press on behalf of the Society for Neuro-Oncology 2015.

STEM-19EGFR EXPRESSION CONFERS STEM CELL-LIKE PROPERTIES TO HUMAN NEURAL PROGENITORS AND GLIOMAS

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STEM-19EGFR EXPRESSION CONFERS STEM CELL-LIKE PROPERTIES TO HUMAN NEURAL PROGENITORS AND GLIOMAS

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