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EphrinB3 and EphrinB4 Receptors are potential therapeutic targets in glioblastoma

Published online by Cambridge University Press:  10 December 2015

R. Sreeraman Kumar
Affiliation:
Department of Radiation Oncology, H.L. Moffitt Cancer Center, Tampa, FL
R.J.B. Macaulay
Affiliation:
Department of Anatomic Pathology, H.L. Moffitt Cancer Center, Tampa, FL
H.C. Rutherford
Affiliation:
Department of Anatomic Pathology, H.L. Moffitt Cancer Center, Tampa, FL
N. Barkey
Affiliation:
Department of Cancer Imaging and Metabolism, H.L. Moffitt Cancer Center, Tampa, FL
J. Koomen
Affiliation:
Department of Molecular Oncology & Proteomics Core, H.L. Moffitt Cancer Center, Tampa, FL
D.L. Morse
Affiliation:
Department of Cancer Imaging and Metabolism, H.L. Moffitt Cancer Center, Tampa, FL
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Abstract

Type
Abstracts
Copyright
Copyright © The Canadian Journal of Neurological Sciences Inc. 2015 

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.