Glioblastoma (GBM) is the most common malignant neoplasm of the central nervous system in adults. Despite advances in surgery, chemotherapy, and radiation technique, median overall survival remains dismal at 5 years after diagnosis. CD133 is a known putative cancer stem cell marker, and we aimed to identify markers in CD133+ GBM tumour initiating cell lines (TICs) with an infiltrative phenotype that could serve as therapeutic targets.

Expression (mRNA) microarray datasets including 22,278 probes for known cell-surface markers in three CD133+TICs and 17 normal brain tissue lines were obtained. By expression profiling, we identified genes with uniformly high mRNA expression, filtered for known localization at the cell-surface, and for non- or low expression in normal brain; amongst the highly expressed were ephrin B3 receptor (EphB3), ephrin B4 receptor (EphB4) and fibroblast growth factor receptor (FGFR1). Protein expression was established by mass spectrometry using CD133+ cell line extracts. These were further evaluated in 27 patient GBM (IDH-wildtype) tumour samples by immunohistochemistry, both in the tumour and at the brain-tumor interface. Expression in >50% of tumour cells was enumerated as 7/27 for EphB3, 8/27 for EphB4, and 18/27 for FGFR1. Most tumours failed to exhibit a gradient of expression across the brain-tumor interface. Expression was occasionally noted in normal-appearing cells, particularly pyramidal neurons; most reactive-appearing astrocytes also strongly expressed FGFR1. Correlation with clinical parameters may disclose subsets of these tumours with varying infiltrative potential.

Conflictsof Interest:

None.