Calcium Signaling in Brain Cancers: Roles and Therapeutic Targeting

Maklad, Ahmed; Sharma, Anjana; Azimi, Iman

doi:10.3390/cancers11020145

Cited by 51 publications

(49 citation statements)

References 98 publications

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“…To our knowledge, this phenomenon has not been previously reported in BMSCs or other cell types. A possible explanation for this discrepancy is the difference in the differentiation state of BMSCs because the effects of intracellular Ca 2+ on cell proliferation are dependent on cell types [30][31][32][33], and we observed that PMA suppresses the adipogenesis of BMSCs. In other words, high Ca 2+ might enhance the proliferation of BMSCs committed to adipocytes and have little effect on the proliferation of uncommitted BMSCs.…”

Section: Discussionmentioning

confidence: 65%

Phorbol 12-myristate 13-acetate (PMA) suppresses high Ca2+-enhanced adipogenesis in bone marrow stromal cells

et al. 2019

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We have previously reported that increased extracellular and intracellular Ca 2+ lead to adipocyte accumulation in bone marrow stromal cells (BMSCs). However, strategies to suppress high Ca 2+-enhanced adipocyte accumulation have not been reported. We examined the effects of the diacylglycerol analog phorbol 12-myristate 13-acetate (PMA) on proliferation and adipogenesis of mouse primary BMSCs. We used 9 mM CaCl 2 and 100 nM ionomycin to increase extracellular Ca 2+ and intracellular Ca 2+ , respectively. PMA suppressed the expression of both C/EBPα and PPARγ under normal adipogenesis, adipogenesis + CaCl 2 , and adipogenesis + ionomycin conditions. PMA enhanced proliferation under normal adipogenesis conditions but suppressed proliferation under adipogenesis + CaCl 2 and adipogenesis + ionomycin conditions. PMA did not affect the accumulation of adipocytes under normal adipogenesis conditions but suppressed adipocyte accumulation under adipogenesis + CaCl 2 and adipogenesis + ionomycin conditions. These results suggest that the PMA-dependent pathway is an important signaling pathway to suppress high Ca 2+-enhanced adipocyte accumulation.

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Section: Discussionmentioning

confidence: 65%

Phorbol 12-myristate 13-acetate (PMA) suppresses high Ca2+-enhanced adipogenesis in bone marrow stromal cells

et al. 2019

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“…The altered expression and activity of specific Ca 2+ channels and pumps have been reported in malignant gliomas [28]. Amlodipine, a commonly used antihypertensive drug, was shown to inhibit tumor growth by the inhibition of YAP/TAZ signaling via the hippo pathway, which is involved in tumor malignancy by the activation of store-operated Ca 2+ entry.…”

Section: Calcium Channel Blockermentioning

confidence: 99%

Drug Repositioning for the Treatment of Glioma: Current State and Future Perspective

Tamai¹,

Hirai²,

Jiapaer³

et al. 2020

Drug Repurposing - Hypothesis, Molecular Aspects and Therapeutic Applications

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Gliomas are the most common primary brain tumors. Among them, glioblastoma (GBM) possesses the most malignant phenotype. Despite the current standard therapy using an alkylating anticancer agent, temozolomide, most patients with GBM die within 2 years. Novel chemotherapeutic agents are urgently needed to improve the prognosis of GBM. One of the solutions, drug repositioning, which broadens the indications of existing drugs, has gained attention. Herein, we categorize candidate agents, which are newly identified as therapeutic drugs for malignant glioma into 10 classifications based on these original identifications. Some drugs are in clinical trials with hope. Additionally, the obstacles, which should be overcome in order to accomplish drug repositioning as an application for GBM and the future perspectives, have been discussed.

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“…Ions channels expressed on glioblastoma cells including various potassium, calcium, sodium, and chloride ion channels are believed to facilitate pathogenesis of glioblastoma 27,[70][71][72] . Although the expressions of numerous ion channels vary among clinical glioma samples 25 , ion channel expression profiles have been suggested to predict survival in glioma patients 73,74 .…”

Section: E Glioblastoma Electrotaxis Is Mediated By Voltage-gated Iomentioning

confidence: 99%

“…VGCCs are known to play important roles in glioma biology such as cell proliferation, apoptosis, and sensitization to ionizing radiation 27,75,76 . VGCCs can be categorized as high voltage activated (HVA) or low voltage activated (LVA) types [77][78][79] .…”

Section: E Glioblastoma Electrotaxis Is Mediated By Voltage-gated Iomentioning

confidence: 99%

“…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%

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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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Calcium Signaling in Brain Cancers: Roles and Therapeutic Targeting

Cited by 51 publications

References 98 publications

Phorbol 12-myristate 13-acetate (PMA) suppresses high Ca2+-enhanced adipogenesis in bone marrow stromal cells

Phorbol 12-myristate 13-acetate (PMA) suppresses high Ca2+-enhanced adipogenesis in bone marrow stromal cells

Drug Repositioning for the Treatment of Glioma: Current State and Future Perspective

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

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