Glioblastoma and calcium signaling - analysis of calcium toolbox expression

Robil, Noémie; Petel, Fabien; Kilhoffer, Marie‐Claude; Haiech, Jacques

doi:10.1387/ijdb.150200jh

Cited by 28 publications

(27 citation statements)

References 34 publications

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“…A similar analysis has been recently carried out in glioblastoma using data gathered from repository data sets of a large series of glioblastomas [23]. Data shown here were generated using Ion Torrent RNA-sequencing from mRNA isolated from normal human colonic NCM460 cells and colon cancer HT29 cells.…”

Section: Resultsmentioning

confidence: 99%

“…However, Ca 2+ remodeling is complex and may involve changes in expression and/or activity of hundreds of genes related to Ca 2+ signaling [23], with nearly 80 of them directly involved in Ca 2+ transport across biological membranes. By taking advantage of Next Generation Sequencing technologies, particularly RNA-sequencing (RNA-seq) by Ion Torrent methodologies, we were able to study in detail intracellular Ca 2+ homeostasis in NCM460 cells reflecting normal human colonic cells [24,25] and HT29 cells [26] representing human colorectal cancer cells, to investigate, for the first time, the transcriptomics of Ca 2+ remodeling in CRC.…”

Section: Introductionmentioning

confidence: 99%

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Transcriptomic Analysis of Calcium Remodeling in Colorectal Cancer

Pérez-Riesgo

Gutiérrez

Ubierna

et al. 2017

IJMS

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Colorectal cancer (CRC) cells undergo the remodeling of intracellular Ca2+ homeostasis, which contributes to cancer hallmarks such as enhanced proliferation, invasion and survival. Ca2+ remodeling includes critical changes in store-operated Ca2+ entry (SOCE) and Ca2+ store content. Some changes have been investigated at the molecular level. However, since nearly 100 genes are involved in intracellular Ca2+ transport, a comprehensive view of Ca2+ remodeling in CRC is lacking. We have used Next Generation Sequencing (NGS) to investigate differences in expression of 77 selected gene transcripts involved in intracellular Ca2+ transport in CRC. To this end, mRNA from normal human colonic NCM460 cells and human colon cancer HT29 cells was isolated and used as a template for transcriptomic sequencing and expression analysis using Ion Torrent technology. After data transformation and filtering, exploratory analysis revealed that both cell types were well segregated. In addition, differential gene expression using R and bioconductor packages show significant differences in expression of selected voltage-operated Ca2+ channels and store-operated Ca2+ entry players, transient receptor potential (TRP) channels, Ca2+ release channels, Ca2+ pumps, Na+/Ca2+ exchanger isoforms and genes involved in mitochondrial Ca2+ transport. These data provide the first comprehensive transcriptomic analysis of Ca2+ remodeling in CRC.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Transcriptomic Analysis of Calcium Remodeling in Colorectal Cancer

Pérez-Riesgo

Gutiérrez

Ubierna

et al. 2017

IJMS

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“…This study highlights the importance of calcium management in radioresistance. Interestingly, a large genomic analysis study demonstrated that GSCs have elevated expression of several key genes related to calcium transport, calcium reuptake, and calcium-responding proteins(68); these results suggest that GSCs may have the ability to resist radiotherapy by more efficient calcium management. Given the importance of calcium levels in radiation induced apoptosis, this theory seems like a promising avenue for further investigation.…”

Section: Calcium Management—an Emerging Influence In Radioresistancementioning

confidence: 99%

Radiotherapy and Glioma Stem Cells: Searching for Chinks in Cellular Armor

2017

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Purpose of the review Radiation became a pillar of oncologic treatment in the last century and provided a powerful and effective locoregional treatment of solid malignancies. After achieving some of the first cures in lymphomas and skin cancers, it assumed a key role in curative treatment of epithelioid malignancies. Despite success across a variety of histologic types, glioblastoma (GBM), the most common primary brain tumor afflicting adults, remains ultimately resistant to current radiation strategies. While GBMs demonstrate an initial response, recurrence is essentially universal and fatal, and typically reoccur in the areas that received the most intense radiation. Recent Findings Glioma stem cells (GSCs), a subpopulation of tumor cells with expression profiles similar to neural stem cells and marked self-renewal capacities, have been shown to drive tumor recurrence and preclude curative radiotherapy. Recent research has shown that these cells have enhanced DNA repair capacity, elevated resistance to cytotoxic ion fluxes and escape multi-modality therapies. Summary We will analyze the current understanding of GSCs and radiation by highlighting key discoveries probing their ability to withstand radiotherapy. We then speculate on novel mechanisms by which GSC can be made sensitive to or specifically targeted by radiation therapy.

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“…Among the voltagegated ion channels in the brain, calcium channels are especially important as calcium influx plays a pivotal role in cellular signaling 21,22 . Calcium signaling is also important in glioma cell proliferation, resistance to therapy, and metastasis [23][24][25][26][27] . Whether or not the calcium signaling in glioma is mediated by electric field is still an open question.…”

Section: Introductionmentioning

confidence: 99%

Voltage-gated ion channels mediate the electrotaxis of glioblastoma cells in a hybrid PMMA/PDMS microdevice

Tsai

IJspeert

Shen

2020

Preprint

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Transformed astrocytes in the most aggressive form cause glioblastoma, the most common cancer in central nervous system with high mortality. The physiological electric field by neuronal local field potentials and tissue polarity may guide the infiltration of glioblastoma cells through the electrotaxis process. However, microenvironments with multiplex gradients are difficult to create. In this work, we have developed a hybrid microfluidic platform to study glioblastoma electrotaxis in controlled microenvironments with high throughput quantitative analysis by a machine learning-powered single cell tracking software. By equalizing the hydrostatic pressure difference between inlets and outlets of the microchannel, uniform single cells can be seeded reliably inside the microdevice. The electrotaxis of two glioblastoma models, T98G and U-251MG, require optimal laminin-containing extracellular matrix and exhibits opposite directional and electro-alignment tendencies. Calcium signaling is a key contributor in glioblastoma pathophysiology but its role in glioblastoma electrotaxis is still an open question. Anodal T98G electrotaxis and cathodal U-251MG electrotaxis require the presence of extracellular calcium cations. U-251MG electrotaxis is dependent on the P/Q-type voltage-gated calcium channel (VGCC) and T98G is dependent on the R-type VGCC. U-251MG and T98G electrotaxis are also mediated by A-type (rapidly inactivating) voltage-gated potassium channels and acidsensing sodium channels. The involvement of multiple ion channels suggests that the glioblastoma electrotaxis is complex and patient-specific ion channel expression can be critical to develop personalized therapeutics to fight against cancer metastasis. The hybrid microfluidic design and machine learning-powered single cell analysis provide a simple and flexible platform for quantitative investigation of complicated biological systems.

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Glioblastoma and calcium signaling - analysis of calcium toolbox expression

Cited by 28 publications

References 34 publications

Transcriptomic Analysis of Calcium Remodeling in Colorectal Cancer

Transcriptomic Analysis of Calcium Remodeling in Colorectal Cancer

Radiotherapy and Glioma Stem Cells: Searching for Chinks in Cellular Armor

Voltage-gated ion channels mediate the electrotaxis of glioblastoma cells in a hybrid PMMA/PDMS microdevice

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