Tunneling nanotubes between rat primary astrocytes and C6 glioma cells alter proliferation potential of glioma cells

Zhang, Lei; Zhang, Yan

doi:10.1007/s12264-014-1522-4

Cited by 65 publications

(66 citation statements)

References 42 publications

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“…As it is reported in literature that TnTs are not observed in some glioma cellular models (Van der Vos et al, 2016), we checked if U87-MG cells and NHA cells herein used were able to form TnTs in vitro. The results showed that both types of cells were able to communicate between them by TnTs, as already reported (Zhang and Zhang, 2015;Rostami et al, 2017;Reindl et al, 2019), and the percentage of cells forming TnTs was similar between U87-MG and NHA cells. As TnTs have been grouped into two main classes, very thin (≤0.7 µm, measuring a minimum of 100-200 nm) and thick (≥0.7 µm, up to 1 µm; Gerdes et al, 2007), we analyzed the heterogeneity of TnTs formed by U87-MG and NHA.…”

Section: Discussionsupporting

confidence: 86%

Differential Exchange of Multifunctional Liposomes Between Glioblastoma Cells and Healthy Astrocytes via Tunneling Nanotubes

Formicola

D’Aloia

Magro

et al. 2019

Front. Bioeng. Biotechnol.

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Despite advances in cancer therapies, nanomedicine approaches including the treatment of glioblastoma (GBM), the most common, aggressive brain tumor, remains inefficient. These failures are likely attributable to the complex and not yet completely known biology of this tumor, which is responsible for its strong invasiveness, high degree of metastasis, high proliferation potential, and resistance to radiation and chemotherapy. The intimate connection through which the cells communicate between them plays an important role in these biological processes. In this scenario, tunneling nanotubes (TnTs) are recently gaining importance as a key feature in tumor progression and in particular in the re-growth of GBM after surgery. In this context, we firstly identified structural differences of TnTs formed by U87-MG cells, as model of GBM cells, in comparison with those formed by normal human astrocytes (NHA), used as a model of healthy cells. Successively, we have studied the possibility to exploit U87-MG TnTs as drug-delivery channels in cancer therapy, using liposomes composed of cholesterol/sphingomyelin and surface functionalized with mApoE and chlorotoxin peptides (Mf-LIP) as nanovehicle model. The results showed that U87-MG cells formed almost exclusively thick and long protrusions, whereas NHA formed more thin and short TnTs. Considering that thick TnTs are more efficient in transport of vesicles and organelles, we showed that fluorescent-labeled Mf-LIP can be transported via TnTs between U87-MG cells and with less extent through the protrusions formed by NHA cells. Our results demonstrate that nanotubes are potentially useful as drug-delivery channels for cancer therapy, facilitating the intercellular redistribution of this drug in close and far away cells, thus reaching isolated tumor niches that are hardly targeted by simple drug diffusion in the brain parenchyma. Moreover, the differences identified in TnTs formed by GBM and NHA cells can be exploited to increase treatment precision and specificity.

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Section: Discussionsupporting

confidence: 86%

Differential Exchange of Multifunctional Liposomes Between Glioblastoma Cells and Healthy Astrocytes via Tunneling Nanotubes

Formicola

D’Aloia

Magro

et al. 2019

Front. Bioeng. Biotechnol.

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“…To test the effect of Wnt7a on TNT formation, CAD cells were treated with increasing concentrations of Wnt7a for 4 h (Fig A). In these experiments, 200 μM of H 2 O 2 treatment was used as a positive control for TNT induction (Gousset et al , ; Zhang & Zhang, ). We found that Wnt7a is able to increase the percentage of TNT‐connected cells in a dose‐dependent manner (Fig A and B).…”

Section: Resultsmentioning

confidence: 99%

The Wnt/Ca ²⁺ pathway is involved in interneuronal communication mediated by tunneling nanotubes

Vargas

Loría

et al. 2019

The EMBO Journal

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Tunneling nanotubes (TNTs) are actin‐based transient tubular connections that allow direct communication between distant cells. TNTs play an important role in several physiological (development, immunity, and tissue regeneration) and pathological (cancer, neurodegeneration, and pathogens transmission) processes. Here, we report that the Wnt/Ca2+ pathway, an intracellular cascade that is involved in actin cytoskeleton remodeling, has a role in TNT formation and TNT‐mediated transfer of cargoes. Specifically, we found that Ca2+/calmodulin‐dependent protein kinase II (CaMKII), a transducer of the Wnt/Ca2+ pathway, regulates TNTs in a neuronal cell line and in primary neurons. We identified the β isoform of CaMKII as a key molecule in modulating TNT formation and transfer, showing that this depends on the actin‐binding activity of the protein. Finally, we found that the transfer of vesicles and aggregated α‐synuclein between primary neurons can be regulated by the activation of the Wnt/Ca2+ pathway. Our findings suggest that Wnt/Ca2+ pathway could be a novel promising target for therapies designed to impair TNT‐mediated propagation of pathogens.

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“…aid glioma cells in infiltrating the surrounding parenchyma. [154][155][156] The expression of connexin 43 (Cx43) 157 and different ATP-dependent ion channels (ClC-3, VGCC, TRPs, hERG, ENaC, CLICs) 158 in reactive astrocytes offer protection against radio-and chemotherapy via activation of Bcl2 family proteins and inhibition of cytochrome c release from mitochondria. 159 It is also reported that reactive astrocytes supply a suitable microenvironment for the transformation of CD133 + glioma stem cells from CD133 − cells.…”

Section: Role Of Neurovascular Unit In Ischemia and Glioma Astrocytesmentioning

confidence: 99%

The interrelationship between cerebral ischemic stroke and glioma: a comprehensive study of recent reports

Ghosh

Chakraborty

Sarkar

et al. 2019

Sig Transduct Target Ther

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Glioma and cerebral ischemic stroke are two major events that lead to patient death worldwide. Although these conditions have different physiological incidences,~10% of ischemic stroke patients develop cerebral cancer, especially glioma, in the postischemic stages. Additionally, the high proliferation, venous thrombosis and hypercoagulability of the glioma mass increase the significant risk of thromboembolism, including ischemic stroke. Surprisingly, these events share several common pathways, viz. hypoxia, cerebral inflammation, angiogenesis, etc., but the proper mechanism behind this co-occurrence has yet to be discovered. The hypercoagulability and presence of the D-dimer level in stroke are different in cancer patients than in the noncancerous population. Other factors such as atherosclerosis and coagulopathy involved in the pathogenesis of stroke are partially responsible for cancer, and the reverse is also partially true. Based on clinical and neurosurgical experience, the neuronal structures and functions in the brain and spine are observed to change after a progressive attack of ischemia that leads to hypoxia and atrophy. The major population of cancer cells cannot survive in an adverse ischemic environment that excludes cancer stem cells (CSCs). Cancer cells in stroke patients have already metastasized, but early-stage cancer patients also suffer stroke for multiple reasons. Therefore, stroke is an early manifestation of cancer. Stroke and cancer share many factors that result in an increased risk of stroke in cancer patients, and vice-versa. The intricate mechanisms for stroke with and without cancer are different. This review summarizes the current clinical reports, pathophysiology, probable causes of co-occurrence, prognoses, and treatment possibilities.

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Tunneling nanotubes between rat primary astrocytes and C6 glioma cells alter proliferation potential of glioma cells

Cited by 65 publications

References 42 publications

Differential Exchange of Multifunctional Liposomes Between Glioblastoma Cells and Healthy Astrocytes via Tunneling Nanotubes

Differential Exchange of Multifunctional Liposomes Between Glioblastoma Cells and Healthy Astrocytes via Tunneling Nanotubes

The Wnt/Ca ²⁺ pathway is involved in interneuronal communication mediated by tunneling nanotubes

The interrelationship between cerebral ischemic stroke and glioma: a comprehensive study of recent reports

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Tunneling nanotubes between rat primary astrocytes and C6 glioma cells alter proliferation potential of glioma cells

Cited by 65 publications

References 42 publications

Differential Exchange of Multifunctional Liposomes Between Glioblastoma Cells and Healthy Astrocytes via Tunneling Nanotubes

Differential Exchange of Multifunctional Liposomes Between Glioblastoma Cells and Healthy Astrocytes via Tunneling Nanotubes

The Wnt/Ca 2+ pathway is involved in interneuronal communication mediated by tunneling nanotubes

The interrelationship between cerebral ischemic stroke and glioma: a comprehensive study of recent reports

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The Wnt/Ca ²⁺ pathway is involved in interneuronal communication mediated by tunneling nanotubes