Reactive Astrocytes in Glioblastoma Multiforme

Guan, Xiudong; Hasan, Nabiul; Maniar, Shelly; Jia, Wang; Sun, Dandan

doi:10.1007/s12035-018-0880-8

Cited by 92 publications

(91 citation statements)

References 122 publications

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“…In the same picture, ion channels and ion transporters, expressed at the membrane of both astrocytes and GBM cells might then form a bridge between the two cellular types, thus enhancing tumor progression and therapeutic resistance, as suggested by a recent review (Guan, Hasan, Maniar, Jia, & Sun, ). Also, the GBM‐derived extracellular vesicles (EVs) might significantly alter the intracellular signaling and cytokine profile of normal human astrocytes to push them towards a tumor supporting behavior (Oushy et al, ).…”

Section: Role Of Astrocytes During Glioblastoma Developmentmentioning

confidence: 94%

Astrocytes, the rising stars of the glioblastoma microenvironment

Brandao

Simon

Critchley

et al. 2018

Glia

141

117

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Glioblastoma (GBM) is an aggressive primary tumor, causing thousands of deaths worldwide every year. The mean survival of patients with GBM remains below 20 months despite current available therapies. GBM cells' interactions with their stromal counterparts are crucial for tumor development. Astrocytes are glial cells that comprise~50% of all brain cells and are therefore likely to establish direct contact with GBM cells. As other tumor cell types can hijack fibroblasts or immune cells to facilitate tumor growth, GBM cells can actually activate astrocytes, namely, the tumor associated astrocytes (TAAs), to promote GBM invasion in the healthy tissue. TAAs have thus been shown to be involved in GBM cells growth and limited response to radiation or chemotherapy (i.e., Temozolomide). Nevertheless, even though the interest in the cancer research community is increasing, the role of TAAs during GBM development is still overlooked.Yet, obtaining an in-depth understanding of the mechanisms by which TAAs influence GBM progression might lead to the development of new therapeutic strategies. This article therefore reports the different levels of GBM progression at which TAAs have been recently described to be involved in, including tumor cells' proliferation/invasion and resistance to therapies, especially through the activity of extracellular vesicles. K E Y W O R D S brain, glioblastoma, stromal cells, tumor associated astrocytes, tumor microenvironment

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Section: Role Of Astrocytes During Glioblastoma Developmentmentioning

confidence: 94%

Astrocytes, the rising stars of the glioblastoma microenvironment

Brandao

Simon

Critchley

et al. 2018

Glia

141

117

View full text Add to dashboard Cite

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“…The different expression of ARG1 and CDH1 in our model might display the limitations of our model but might also indicate that these characteristics are dependent on other components of the TME. [12,22] By implementing other cell types in our model, for instance glioma-associated astrocytes, which so far have not been fully investigated for their contribution to GBM, [23] and by gradually increasing the complexity of this model, it might be possible to clearly and specifically define the function and contribution from each TME component. To further confirm the clinical significance of the aforementioned genes, we analyzed the survival of 577 GBM patients.…”

Section: (Supplementary Figure S4c and S4d)mentioning

confidence: 99%

3D‐Bioprinted Mini‐Brain: A Glioblastoma Model to Study Cellular Interactions and Therapeutics

et al. 2019

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Glioblastoma-associated macrophages (GAMs) play a crucial role in the progression and invasiveness of glioblastoma multiforme (GBM); however, the exact crosstalk between GAMs and glioblastoma cells is not fully understood. Furthermore, there is a lack of relevant in vitro models to mimic their interactions. Here, novel 3D-bioprinted mini-brains consisting of glioblastoma cells and macrophages are presented as tool to study the interactions between these two cell types and to test therapeutics that target this interaction. It is demonstrated that in the mini-brains, glioblastoma cells actively recruit macrophages and polarize them into a GAM-specific phenotype, showing clinical relevance to transcriptomic and patient survival data. Furthermore, it is shown that macrophages induce glioblastoma cell progression and invasiveness in the mini-brains. Finally, it is demonstrated how therapeutics can inhibit the interaction between GAMs and tumor cells resulting in reduced tumor growth and more sensitivity to chemotherapy. It is envisioned that this 3D-bioprinted tumor model is used to improve the understanding of tumor biology and for evaluating novel cancer therapeutics.

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“…Differential expression of hEAG1 and hERG1 is found amongst gliomas conferring to the malignant status and nature of the tumour. Kv11.1 is associated with abnormal expression in hGG [ 85 ]. Similarly, when supressed by siRNA hERG mediated apoptosis in glioma cell lines demonstrating a key role in glioma apoptosis [ 86 ].…”

Section: Ion Channels In Gliomamentioning

confidence: 99%

Ion Channels as Therapeutic Targets in High Grade Gliomas

Griffin

Khan

Basu

et al. 2020

Cancers

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Glioblastoma multiforme (GBM) is a lethal brain cancer with an average survival of 14–15 months even with exhaustive treatment. High grade gliomas (HGG) represent the leading cause of CNS cancer-related death in children and adults due to the aggressive nature of the tumour and limited treatment options. The scarcity of treatment available for GBM has opened the field to new modalities such as electrotherapy. Previous studies have identified the clinical benefit of electrotherapy in combination with chemotherapeutics, however the mechanistic action is unclear. Increasing evidence indicates that not only are ion channels key in regulating electrical signaling and membrane potential of excitable cells, they perform a crucial role in the development and neoplastic progression of brain tumours. Unlike other tissue types, neural tissue is intrinsically electrically active and reliant on ion channels and their function. Ion channels are essential in cell cycle control, invasion and migration of cancer cells and therefore present as valuable therapeutic targets. This review aims to discuss the role that ion channels hold in gliomagenesis and whether we can target and exploit these channels to provide new therapeutic targets and whether ion channels hold the mechanistic key to the newfound success of electrotherapies.

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Reactive Astrocytes in Glioblastoma Multiforme

Cited by 92 publications

References 122 publications

Astrocytes, the rising stars of the glioblastoma microenvironment

Astrocytes, the rising stars of the glioblastoma microenvironment

3D‐Bioprinted Mini‐Brain: A Glioblastoma Model to Study Cellular Interactions and Therapeutics

Ion Channels as Therapeutic Targets in High Grade Gliomas

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