Influence of α-Particle Radiation on Intercellular Communication Networks of Tunneling Nanotubes in U87 Glioblastoma Cells

Matejka, Nicole; Reindl, Judith

doi:10.3389/fonc.2020.01691

Cited by 17 publications

(11 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In 1992, Nagasawa and Little were the first to show the involvement of bystander effects in alpha particle irradiation in CHO cells irradiated with low fluences of alpha particles produced by 238 Pu (57). Their findings were confirmed and expanded by many other researchers (58)(59)(60)(61). They observed that sister chromatid exchanges were increased in 30% of cells, although only 1% of nuclei were traversed by particles.…”

Section: Revisiting the Target Cell Theory: Involvement Of Bystander Effectssupporting

confidence: 75%

Revisiting the Radiobiology of Targeted Alpha Therapy

Pouget

Constanzo

2021

Front. Med.

View full text Add to dashboard Cite

Targeted alpha therapy (TAT) using alpha particle-emitting radionuclides is in the spotlight after the approval of 223RaCl2 for patients with metastatic castration-resistant prostate cancer and the development of several alpha emitter-based radiopharmaceuticals. It is acknowledged that alpha particles are highly cytotoxic because they produce complex DNA lesions. Hence, the nucleus is considered their critical target, and many studies did not report any effect in other subcellular compartments. Moreover, their physical features, including their range in tissues (<100 μm) and their linear energy transfer (50–230 keV/μm), are well-characterized. Theoretically, TAT is indicated for very small-volume, disseminated tumors (e.g., micrometastases, circulating tumor cells). Moreover, due to their high cytotoxicity, alpha particles should be preferred to beta particles and X-rays to overcome radiation resistance. However, clinical studies showed that TAT might be efficient also in quite large tumors, and biological effects have been observed also away from irradiated cells. These distant effects are called bystander effects when occurring at short distance (<1 mm), and systemic effects when occurring at much longer distance. Systemic effects implicate the immune system. These findings showed that cells can die without receiving any radiation dose, and that a more complex and integrated view of radiobiology is required. This includes the notion that the direct, bystander and systemic responses cannot be dissociated because DNA damage is intimately linked to bystander effects and immune response. Here, we provide a brief overview of the paradigms that need to be revisited.

show abstract

Section: Revisiting the Target Cell Theory: Involvement Of Bystander Effectssupporting

confidence: 75%

Revisiting the Radiobiology of Targeted Alpha Therapy

Pouget

Constanzo

2021

Front. Med.

View full text Add to dashboard Cite

show abstract

“…Interestingly, we recently showed that TNTs formed by healthy astrocytes or by GBM cells display structural differences in terms of length and thickness, which reflect different transport efficiencies [123]. A recent paper showed that irradiated U87 GBM cells quickly establish a network of cell-to-cell connections with high TNT content in comparison with non-irradiated cells, suggesting that the TNT formation may be also a consequence of treatment [124].…”

Section: Formation Of Tnts In Gbmmentioning

confidence: 99%

The 3.0 Cell Communication: New Insights in the Usefulness of Tunneling Nanotubes for Glioblastoma Treatment

Taiarol

Formicola

Fagioli

et al. 2021

Cancers

View full text Add to dashboard Cite

Glioblastoma (GBM) is a particularly challenging brain tumor characterized by a heterogeneous, complex, and multicellular microenvironment, which represents a strategic network for treatment escape. Furthermore, the presence of GBM stem cells (GSCs) seems to contribute to GBM recurrence after surgery, and chemo- and/or radiotherapy. In this context, intercellular communication modalities play key roles in driving GBM therapy resistance. The presence of tunneling nanotubes (TNTs), long membranous open-ended channels connecting distant cells, has been observed in several types of cancer, where they emerge to steer a more malignant phenotype. Here, we discuss the current knowledge about the formation of TNTs between different cellular types in the GBM microenvironment and their potential role in tumor progression and recurrence. Particularly, we highlight two prospective strategies targeting TNTs as possible therapeutics: (i) the inhibition of TNT formation and (ii) a boost in drug delivery between cells through these channels. The latter may require future studies to design drug delivery systems that are exchangeable through TNTs, thus allowing for access to distant tumor niches that are involved in tumor immune escape, maintenance of GSC plasticity, and increases in metastatic potential.

show abstract

“…Tissue damage, localized at a drug injection site or to the larger area of tumor resection, was also identified as sufficient cellular stress to trigger TNT formation [ 31 , 47 ]. Moreover, cancer therapy itself can constitute a tissue insult sufficient to stimulate TNT formation, as shown following α-particle radiation of U87 glioblastoma cell line or doxorubicin, cytarabine and temozolomide chemotherapeutic treatments in human pancreatic cell lines, human AML blasts and human glioblastoma cell lines respectively [ 33 , 48 , 68 , 69 ].…”

Section: Molecular Determinants Of Tnt Formation and Cargo Intercellu...mentioning

confidence: 99%

Intercellular Communication in the Brain through Tunneling Nanotubes

Khattar

Safi

Rodriguez

et al. 2022

Cancers

View full text Add to dashboard Cite

Intercellular communication is essential for tissue homeostasis and function. Understanding how cells interact with each other is paramount, as crosstalk between cells is often dysregulated in diseases and can contribute to their progression. Cells communicate with each other through several modalities, including paracrine secretion and specialized structures ensuring physical contact between them. Among these intercellular specialized structures, tunneling nanotubes (TNTs) are now recognized as a means of cell-to-cell communication through the exchange of cellular cargo, controlled by a variety of biological triggers, as described here. Intercellular communication is fundamental to brain function. It allows the dialogue between the many cells, including neurons, astrocytes, oligodendrocytes, glial cells, microglia, necessary for the proper development and function of the brain. We highlight here the role of TNTs in connecting these cells, for the physiological functioning of the brain and in pathologies such as stroke, neurodegenerative diseases, and gliomas. Understanding these processes could pave the way for future therapies.

show abstract

Influence of α-Particle Radiation on Intercellular Communication Networks of Tunneling Nanotubes in U87 Glioblastoma Cells

Cited by 17 publications

References 37 publications

Revisiting the Radiobiology of Targeted Alpha Therapy

Revisiting the Radiobiology of Targeted Alpha Therapy

The 3.0 Cell Communication: New Insights in the Usefulness of Tunneling Nanotubes for Glioblastoma Treatment

Intercellular Communication in the Brain through Tunneling Nanotubes

Contact Info

Product

Resources

About