Distinct pools of cancer stem-like cells coexist within human glioblastomas and display different tumorigenicity and independent genomic evolution

Abstract

Glioblastomas (GBMs) contain transformed, self-maintaining, multipotent, tumour-initiating cancer stem cells, whose identification has radically changed our perspective on the physiology of these tumours. Currently, it is unknown whether multiple types of transformed precursors, which display alternative sets of the complement of properties of true cancer stem cells, can be found in a GBM. If different subsets of such cancer stem-like cells (CSCs) do exist, they might represent distinct cell targets, with a differential therapeutic importance, also depending on their characteristics and lineage relationship. Here, we report the presence of two types of CSCs within different regions of the same human GBM. Cytogenetic and molecular analysis shows that the two types of CSCs bear quite diverse tumorigenic potential and distinct genetic anomalies, and, yet, derive from common ancestor cells. This provides critical information to unravel the development of CSCs and the key molecular/genetic components underpinning tumorigenicity in human GBMs.

Understanding cancer stem cell heterogeneity and plasticity

“…CSCs have been reported in brain tumors, especially in glioblastoma multiforme (GBM) [61][62][63][64][65][66][67][68][69][70][71][72][73][74]. The stemlike GBM cells have been enriched using cell surface molecules, such as CD133 [61,72], SSEA-1 (stagespecific embryonic antigen-1) [64], EGFR [67,68], and CD44 [69], or functional assays, including the SP analysis [7,63,73] and neurosphere assays [49,74].…”

The future of neuro-oncology

“…4 Photograph of two nuclei (arrows) from a glioma cell (red) and a normal astrocyte (unlabeled). Nanoparticles (green) carrying a tumor-specific antibody bind with the tumor cell and not the astrocyte stem cells that are more resistant to radiotherapy and chemotherapy than the more lineage-defined cells [11,13,14,19,23]. These stem cells may be a source of gliomas and may be one of the reasons these tumors fail to respond more effectively to current treatment.…”

Stem Cells, Radial Glial Cells, and a Unified Origin of Brain Tumors

“…5,6 In contrast, the pathologic substrates of DAWM abnormalities have been investigated only recently. 1,4 Moore et al 1 demonstrated a loss of myelin phospholipids as well as axonal reduction whose extents are intermediate between those of discrete lesions and NAWM.…”

“…Inhibitors of this secretase are being tried in patients with leukemia and are being considered for treatment of children with advanced ependymoma within the US Pediatric Brain Tumor Consortium. [1][2][3][4][5] Conventional therapies tend to kill normal and tumor cells but not the resistant brain tumor stem cells that eventually regenerate the tumor (this is the reason why glioblastomas always recur). In addition, the effect of conventional therapies on tumor cells is limited as they cannot effectively target all of the different cell lineages.…”

“…5 Stem cells may bypass this sequence to produce tumors with single and multiple cell lineages (ie, tumors arise directly from stem cells). If differentiated, tumor cells tend to give origin to brain tumors with a single lineage, but they may undergo dedifferentiation and produce tumors with multiple cell lineages.…”