A paired comparison between glioblastoma “stem cells” and differentiated cells

Abstract

Cancer stem cells (CSC) have been postulated to be responsible for the key features of a malignancy and its maintenances, as well as therapy resistance, while differentiated cells are believed to make up the rapidly growing tumour bulk. It is therefore important to understand the characteristics of those two distinct cell populations in order to devise treatment strategies which effectively target both cohorts, in particular with respect to cancers, such as glioblastoma. Glioblastoma is the most common primary brain tumour in adults, with a mean patient survival of 12-15 months. Importantly, therapeutic improvements have not been forthcoming in the last decade. In this study we compare key features of three pairs of glioblastoma cell populations, each pair consisting of stem cell-like and differentiated cells derived from an individual patient. Our data suggest that while growth rates and expression of key survival-and apoptosis-mediating proteins are more similar according to differentiation status than genetic similarity, we found no intrinsic differences in response to standard therapeutic interventions, namely exposure to radiation or the alkylating agent temozolomide. Interestingly, we could demonstrate that both stem celllike and differentiated cells possess the ability to form stem cell-containing tumours in immunocompromised mice and that differentiated cells could potentially be dedifferentiated to potential stem cells. Taken together our data suggest that the differences between tumour stem cell and differentiated cell are particular fluent in glioblastoma.

Cancer stem cells: The potential role of autophagy, proteolysis, and cathepsins in glioblastoma stem cells

“…142 These cells, termed SC35, SC38, and SC40, were obtained from two male patients and one female patient, between the ages of 44 and 75 years at the time of diagnosis, and are shown to grow invasive in our murine xenotransplant model. 28 The general observation that high CatB levels are characteristic for glioblastoma cells 138 was confirmed in glioblastoma stem cells from several patients (SC35, 38, and 40), differentiated glioblastoma cells (PC35, 38, and 40), and glioblastoma cell lines (A172, U87). 143 Similar to CatB, levels of CatL are higher in glioblastoma cells and responsible for glioblastoma cell invasion.…”

“…116,117 Glioblastoma stem cells are suggested to emerge from neural stem cells or partially from differentiated progenitor cells and are characterized by stem cell markers, such as Sox-2, Nestin, Musashi, and the disputed CD133. However, the latter certainly does not identify the most stem cell-like population in glioblastoma, 118,119 and recent work of Schneider et al 28 shows that a high-level state of plasticity exists between the stem cell and differentiated phenotypes. Nevertheless, glioblastoma stem cells are highly resistant to treatment, partially due to the high expression of the multidrug resistance ABC transporter protein breakpoint cluster region pseudogene 1 (BCRP1), DNA repair proteins, and gene products that inhibit apoptosis.…”

“…While it has been proposed that the cells of origin are tissue stem cells or progenitor cells, 24,25 this view is not universally accepted 26 and recent modeling data can be seen to support the notion that any tissue cell should be drawn as putative cell of origin giving rise to CSCs. 27 An alternative model, shown by us 28 and others [29][30][31] to be potentially applicable for glioblastoma stem cells, postulates that differentiated (tumor) cells can de-differentiate to stem cells, in essence completely separating the concepts of CSCs and cell of origin. Interestingly, while de-differentiation has also been observed to occur in normal tissue cells, 32 it takes place at a much higher frequency within populations of differentiated cancer cells.…”

Exogenous cathepsin G upregulates cell surface MHC class I molecules on immune and glioblastoma cells

“…35, 38, or 40) was minced, washed in PBS, and incubated with TrypLE Express (Gibco, Life Technologies). Cells were filtered and cultured in DMEM/F-12 medium (Gibco, Life Technologies) containing L-glutamine, 0.01% (v/v) epidermal growth factor (EGF, Biomol GmbH, Hamburg, Germany), 0.04% (v/v) fibroblast growth factor (FGF, Miltenyi Biotec, Bergisch Gladbach, Germany), 1% (v/v) B27 (Gibco, Life Technologies), 2% Fungizone (Gibco, Life Technologies), 1% penicillin (120 mg/ml)/streptomycin (120 mg/ml) (Life Technologies) [33]. These cells are herein determined as a sphere-cultured stem cell-enriched glioblastoma cell populations (SCs).…”

Estudos fotofísicos e fotobiológicos de sistemas de liberação contendo o fármaco fotossensível cloro-ftalocianina de alumínio para aplicação em terapia fotodinâmica

“…Esse tipo de patologia é sempre associado a um prognóstico ruim, podendo acometer qualquer parte do tecido cerebral e da medula espinhal, e a uma expectativa de vida muito curta entre 12 e 15 meses (ROBERTS et al, 2011;SCHNEIDER et al, 2016). Como opção mais utilizada de tratamento, adota-se ressecção cirúrgica, seguida por tratamento com radiação e quimioterapia com Temozolamida, que combinadas conferem um período médio de sobrevivência do paciente de até 14,6 meses (STUPP , MASON e VAN DEN BEUF, 2005;ZHANG et al, 2016).…”