Glycosylation-related gene expression is linked to differentiation status in glioblastomas undifferentiated cells

Abstract

Glioblastoma Multiforme (GBM) is the most frequent malignant brain tumor with still poor prognosis. Tumor initiation, growth and recurrences might depend on Brain Tumor Stem Cells (BTSCs) which can promote tumor aggressiveness and potentially affords new therapeutic target. Recent works emphasized aberrant cell-surface glyco-conjugate expression in brain tumors suggesting that altered glycosylation is closely linked to cancer tumor metastasis and invasive process. Post-translational changes might play a key role in determining the fates of most aggressive and undifferentiated cells such as self-renewal, proliferation and differentiation. In order to characterize the glycosylation-related genes involved in differentiation status of the BTSCs, two glioblastoma cell lines, U87-MG and U251 have been cultured according to two conditions leading to undifferentiated floating cells or differentiated adherent cells. The expression level of 559 glycosylation related genes has been analyzed by Taqman Low Density Array (TLDA) analysis and allowed to isolate eight up-regulated genes specific of a subpopulation of undifferentiated cells. Protein expression has been confirmed. Among main selected genes, five are also over-expressed in the undifferentiated condition in primary cultures provided by three GBM freshly isolated from patient. This work suggests that new Glycosylation-related gene signature might improve the characterization of the most aggressive and undifferentiated cells and supports that in future, N-linked glycosylation might provide new target to develop therapeutic strategy for inhibiting tumor growth.