A slow-cycling/quiescent cells subpopulation is involved in glioma invasiveness

Antonica, Francesco; Santomaso, Lucia; Pernici, Davide; Petrucci, Linda; Aiello, Giuseppe; Cutarelli, Alessandro; Conti, Luciano; Romanel, Alessandro; Miele, Evelina; Tebaldi, Toma; Tiberi, Luca

doi:10.1038/s41467-022-32448-0

Cited by 38 publications

(32 citation statements)

References 38 publications

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“…Proliferation and quiescence represent two critical cellular states in normal stem cells [ 2 , 37 ] but also in CSC, in which quiescence has been long considered as a stem-like phenotype involved in tumor propagation and resistance to treatment [ 2 , 3 , 13 , 25 , 42 , 49 ]. To observe and quantify the non-dividing, quiescent cells, we employed a CellTrace labelling assay.…”

Section: Resultsmentioning

confidence: 99%

Comprehensive profiling of stem-like features in pediatric glioma cell cultures and their relation to the subventricular zone

Da-Veiga

Coppieters

Lombard

et al. 2023

acta neuropathol commun

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Pediatric high-grade gliomas (pHGG) are brain tumors occurring in children and adolescents associated with a dismal prognosis despite existing treatments. Therapeutic failure in both adult and pHGG has been partially imputed to glioma stem cells (GSC), a subset of cancer cells endowed with stem-like cell potential and malignant, invasive, adaptative, and treatment-resistant capabilities. Whereas GSC have largely been portrayed in adult tumors, less information has been provided in pHGG. The aim of our study was to comprehensively document the stem-like capacities of seven in-use pediatric glioma cell cultures (Res259, UW479, SF188, KNS42, SF8628, HJSD-DIPG-007 and HJSD-DIPG-012) using parallel in vitro assays assessing stem cell-related protein expression, multipotency, self-renewal and proliferation/quiescence, and in vivo investigation of their tumorigenicity and invasiveness. Data obtained from in vitro experiments revealed glioma subtype-dependent expression of stem cell-related markers and varying abilities for differentiation, self-renewal, and proliferation/quiescence. Among tested cultures, DMG H3-K27 altered cultures displayed a particular pattern of stem-like markers expression and a higher fraction of cells with self-renewal potential. Four cultures displaying distinctive stem-like profiles were further tested for their ability to initiate tumors and invade the brain tissue in mouse orthotopic xenografts. The selected cell cultures all showed a great tumor formation capacity, but only DMG H3-K27 altered cells demonstrated a highly infiltrative phenotype. Interestingly, we detected DMG H3-K27 altered cells relocated in the subventricular zone (SVZ), which has been previously described as a neurogenic area, but also a potential niche for brain tumor cells. Finally, we observed an SVZ-induced phenotypic modulation of the glioma cells, as evidenced by their increased proliferation rate. In conclusion, this study recapitulated a systematic stem-like profiling of various pediatric glioma cell cultures and call to a deeper characterization of DMG H3-K27 altered cells nested in the SVZ.

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Section: Resultsmentioning

confidence: 99%

Comprehensive profiling of stem-like features in pediatric glioma cell cultures and their relation to the subventricular zone

Da-Veiga

Coppieters

Lombard

et al. 2023

acta neuropathol commun

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“…In contrast, gliomas that do not have IDH mutation express higher levels of CD133 and SOX2, the stem cell markers 36 . CD133 expression causes quiescence in glioma cells 37 . Thus, LDH-A activity in IDH-wild type gliomas is involved in conferring stemness and quiescence by increasing lactate production (k4) due to the LDH-A activity and oxidative phosphorylation (kd2) due to the IDH activity.…”

Section: Cell Quiescence Requires a Higher Level Of Oxidative Phospho...mentioning

confidence: 99%

A negative feedback loop underlies the Warburg effect

Singh,

Jaiswal

2023

Preprint

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Aerobic glycolysis, or the Warburg effect, is used by cancer cells for proliferation while producing lactate. Although lactate production has wide implications for cancer progression, it is not known how this effect increases cell proliferation and relates to oxidative phosphorylation. Here, we elucidate that a negative feedback loop (NFL) is responsible for the Warburg effect. Further, we show that aerobic glycolysis works as an amplifier of oxidative phosphorylation. On the other hand, quiescence is an important property of cancer stem cells. Based on the NFL, we show that both aerobic glycolysis and oxidative phosphorylation, playing a synergistic role, are required to achieve cell quiescence. Further, our results suggest that the cells in their hypoxic niche are highly proliferative yet close to attaining quiescence by increasing their NADH/NAD + ratio through the severity of hypoxia. The findings of this study can help in a better understanding of the link among metabolism, cell cycle, carcinogenesis, and stemness.

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“…The proliferation kinetics of cancer stem cells often differ from those of other cells within the tumour and can range from being fast-cycling, slow-cyclin or quiescent 9,10 . In GBM there is a need to characterize how these properties relate to invasiveness of the tumour 11 and to consider the consequence of targeting cycling GSCs on the long-term therapy response of the tumour 12 .…”

Section: Introductionmentioning

confidence: 99%

Profiling Glioma Stem Cell Dynamics via 3D-based Cell Cycle Reporter Assays

Lubanska,

Roye-Azar,

Alrashed

et al. 2024

Preprint

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SummarySuccessful containment of unwanted cell cycle progression in tumours such as glioblastoma (GBM) requires targeted therapeutic approaches which rely on understanding cell cycle dynamics in response to microenvironmental stimuli. Glioma Stem Cells (GSCs) can drive tumour initiation, recurrence, therapy resistance, and are often attributed to the heterogeneity and plasticity of GBM.In vitromodels using patient-derived GSCs provide a life relevant tool for exploration of complex molecular mechanisms underlying the aggressive characteristics of GBM. Introduction of 3D tissue culture systems permits the study of spatial complexity of the tumour mass and enables control over diverse conditions within the surrounding microenvironment. This chapter demonstrates detailed methods to study spatio-temporal changes to the cell cycle dynamics using available fluorescent cell cycle reporter systems in combination with bioinformatics-based signal intensity and localization analysis. We present a successful approach that investigates the 3D cell cycle dynamics of GSC populations. This approach utilizes GBM neurosphere and organoid cultures, which are assessed over time and under therapeutic pressure. These models can be further explored, manipulated, and customized to serve specific experimental designs.

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A slow-cycling/quiescent cells subpopulation is involved in glioma invasiveness

Cited by 38 publications

References 38 publications

Comprehensive profiling of stem-like features in pediatric glioma cell cultures and their relation to the subventricular zone

Comprehensive profiling of stem-like features in pediatric glioma cell cultures and their relation to the subventricular zone

A negative feedback loop underlies the Warburg effect

Profiling Glioma Stem Cell Dynamics via 3D-based Cell Cycle Reporter Assays

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