Calcium Channels in Adult Brain Neural Stem Cells and in Glioblastoma Stem Cells

Coronas, Valérie; Terrié, Elodie; Déliot, Nadine; Arnault, Patricia; Constantin, Bruno

doi:10.3389/fncel.2020.600018

Cited by 12 publications

(11 citation statements)

References 252 publications

(316 reference statements)

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“…These data further indicate that at least a part of the calcitriol-effect is mediated via Ca 2+ signaling. Following this line-of-thought has been shown that Ca 2+ is central to the maintenance of neural stem cells, and it is often aberrantly regulated in GSCs [ 65 ]. Recently, the term calcium toolbox was proposed for the summary of all Ca 2+ -related proteins in a cell, and it was shown that GBM cells have a different composition of this toolbox compared to healthy brain tissue [ 66 ].…”

Section: Discussionmentioning

confidence: 99%

Calcitriol Promotes Differentiation of Glioma Stem-Like Cells and Increases Their Susceptibility to Temozolomide

Gerstmeier

Possmayer

Bozkurt

et al. 2021

Cancers

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Glioblastoma (GBM) is the most common and most aggressive primary brain tumor, with a very high rate of recurrence and a median survival of 15 months after diagnosis. Abundant evidence suggests that a certain sub-population of cancer cells harbors a stem-like phenotype and is likely responsible for disease recurrence, treatment resistance and potentially even for the infiltrative growth of GBM. GBM incidence has been negatively correlated with the serum levels of 25-hydroxy-vitamin D3, while the low pH within tumors has been shown to promote the expression of the vitamin D3-degrading enzyme 24-hydroxylase, encoded by the CYP24A1 gene. Therefore, we hypothesized that calcitriol can specifically target stem-like glioblastoma cells and induce their differentiation. Here, we show, using in vitro limiting dilution assays, quantitative real-time PCR, quantitative proteomics and ex vivo adult organotypic brain slice transplantation cultures, that therapeutic doses of calcitriol, the hormonally active form of vitamin D3, reduce stemness to varying extents in a panel of investigated GSC lines, and that it effectively hinders tumor growth of responding GSCs ex vivo. We further show that calcitriol synergizes with Temozolomide ex vivo to completely eliminate some GSC tumors. These findings indicate that calcitriol carries potential as an adjuvant therapy for a subgroup of GBM patients and should be analyzed in more detail in follow-up studies.

show abstract

Section: Discussionmentioning

confidence: 99%

Calcitriol Promotes Differentiation of Glioma Stem-Like Cells and Increases Their Susceptibility to Temozolomide

Gerstmeier

Possmayer

Bozkurt

et al. 2021

Cancers

View full text Add to dashboard Cite

show abstract

“…These data further indicate that at least a part of the calcitriol-effects is mediated via Ca 2+ -signaling. Following this line-of-thought has been shown that Ca 2+ is central to the maintenance of neural stem cells and often aberrantly regulated in GSCs [65]. Recently, the term calcium toolbox was proposed for the summary of all Ca 2+ -related proteins in a cell and it was shown that GBM cells have a different composition of this toolbox compared to healthy brain tissue [66].…”

Section: Discussionmentioning

confidence: 99%

Calcitriol Promotes Differentiation of Glioma Stem-Like Cells and Increases their Susceptibility to Temozolomide

Gerstmeier¹,

Possmayer²,

Bozkurt³

et al. 2021

Preprint

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: Glioblastoma (GBM) is the most common and most aggressive primary brain tumor with a very high rate of recurrence and a median survival of 15 months after diagnosis. Abundant evi-dence suggests that a certain sub-population of cancer cells harbors a stem-like phenotype and is likely responsible for disease recurrence, treatment resistance and potentially even for the infil-trative growth of GBM. GBM incidence has been negatively correlated with the serum levels of 25-hydroxy-vitamin D3, while the low pH within tumors has been shown to promote the ex-pression of the vitamin D3-degrading enzyme 24-hydroxylase, encoded by the CYP24A1 gene. Therefore, we hypothesized that calcitriol can specifically target stem-like glioblastoma cells and induce their differentiation. Here, we show using in vitro limiting dilution assays, quantita-tive real-time PCR and ex vivo adult organotypic brain slice transplantation cultures that thera-peutic doses of calcitriol, the hormonally active form of vitamin D3, reduces stemness to varying extent in a panel of investigated GSC lines and effectively hinders tumor growth of responding GSCs ex vivo. We further show that calcitriol synergizes with Temozolomide ex vivo to com-pletely eliminate some GSC tumors. These findings indicate that calcitriol carries potential as an adjuvant therapy for a subgroup of GBM patients and should be analyzed in more detail in fol-low-up studies.

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“…S7), suggesting the possibility that TRPV4 activation could also modulate neurogenesis in these regions. Previous findings showing that TRPV4 regulates the fate of mesenchymal stem cells through volume expansion (27) and that TRPV channels mediate spontaneous Ca 2+ signaling in neural stem/progenitor cells (28,29) support this hypothesis. In addition, it is possible that TRPV4 also controls neurogenesis through mechanical stimuli, because cell proliferation is accompanied by transformation of cell membrane.…”

Section: Discussionmentioning

confidence: 84%

Thermosensitive receptors in neural stem cells link stress-induced hyperthermia to impaired neurogenesis via microglial engulfment

et al. 2021

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Calcium Channels in Adult Brain Neural Stem Cells and in Glioblastoma Stem Cells

Cited by 12 publications

References 252 publications

Calcitriol Promotes Differentiation of Glioma Stem-Like Cells and Increases Their Susceptibility to Temozolomide

Calcitriol Promotes Differentiation of Glioma Stem-Like Cells and Increases Their Susceptibility to Temozolomide

Calcitriol Promotes Differentiation of Glioma Stem-Like Cells and Increases their Susceptibility to Temozolomide

Thermosensitive receptors in neural stem cells link stress-induced hyperthermia to impaired neurogenesis via microglial engulfment

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