Journal of Carcinogenesis & Mutagenesis

Abstract

Identification of Glioma Stem Cells: What is Already Known and How Far do We Still Need to Go? The Biomarkers Dilemma

Paola Brescia, Cristina Richichi and Giuliana Pelicci

Cancer stem cells (CSCs) have been isolated in multiple tumour types and although the presence of surface markers selectively expressed on CSCs can be used to isolate these cells, no marker or pattern of markers are sufficiently robust to definitively identify CSCs. Several markers have been evaluated for their prognostic value with promising early results, however to date none has been proven to be clinically useful in large-scale studies. A major need exists to identify markers of CSCs for glioblastoma (GBM), which would yield new therapeutic interventions. Given the complex genetic and epigenetic heterogeneity of human GBMs, it is unlikely that the expression of a single marker will define CSCs in every tumour, hence a combination of markers will probably best define glioma tumour stem cells. The studies reported in the literature regarding the identification of specific cell surface markers involved in tumourigenic processes of the GBM tumour-initiating cells have been inconclusive. Further investigations are necessary to identify both CSC-specific markers and the molecular mechanism sustaining the tumourigenic potential of these cells in order to develop novel treatments to target this group of cells. Markers for GBM stem cells such as CD133, CD15, integrin α6, L1CAM, are available and might be informative to identify these cells but cannot be conclusively linked to a stem cell phenotype. Overlap of expression, functional state and morphology of different subpopulations lead us to reconsider, or carefully consider, the techniques employed so far to characterize cancer stem cells. Major effort might be exploited to look for alternative methods, to isolate CSCs independently from markers. Due to a dearth of methods and markers that reliably assay the function of candidate stem cells, the isolation/enrichment of tumoural stem cells to be therapeutically targeted remains a major challenge.