Tunneling Nanotubes: The Fuel of Tumor Progression?

Pinto, Giulia; Brou, Christel; Zurzolo, Chiara

doi:10.1016/j.trecan.2020.04.012

“…Another mechanism of intercellular communication that has been recently proposed to facilitate tumor progression is represented by Tunneling Nanotubes (TNTs) [13,14]. TNTs are thin cellular extensions connecting distant cells observed in a wide variety of cellular and murine models as well as in ex vivo resections from human tumoral tissue [13].…”

Section: Introductionmentioning

confidence: 99%

“…Another mechanism of intercellular communication that has been recently proposed to facilitate tumor progression is represented by Tunneling Nanotubes (TNTs) [13,14]. TNTs are thin cellular extensions connecting distant cells observed in a wide variety of cellular and murine models as well as in ex vivo resections from human tumoral tissue [13]. They are membranous structures supported by an actin-based cytoskeleton and, differently from other cellular protrusions, including TMs (assumed to provide communication through GAP-junction), are open at both extremities, thus allowing cytoplasmic continuity between connected cells [15,16].…”

Section: Introductionmentioning

confidence: 99%

Patient-derived glioblastoma stem cells transfer mitochondria through tunneling nanotubes in tumor organoids

Pinto

¹

,

Saenz-de-Santa-Maria

²

,

Chastagner

³

et al. 2021

Biochemical Journal

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Glioblastoma (GBM) is the most aggressive brain cancer and its relapse after surgery, chemo and radiotherapy appears to be led by GBM stem cells (GSLCs). Also, tumor networking and intercellular communication play a major role in driving GBM therapy-resistance. Tunneling Nanotubes (TNTs), thin membranous open-ended channels connecting distant cells, have been observed in several types of cancer, where they emerge to drive a more malignant phenotype. Here, we investigated whether GBM cells are capable to intercommunicate by TNTs. Two GBM stem-like cells (GSLCs) were obtained from the external and infiltrative zone of one GBM from one patient. We show, for the first time, that both GSLCs, grown in classical 2D culture and in 3D-tumor organoids, formed functional TNTs which allowed mitochondria transfer. In the organoid model, recapitulative of several tumor’s features, we observed the formation of a network between cells constituted of both Tumor Microtubes (TMs), previously observed in vivo, and TNTs. In addition, the two GSLCs exhibited different responses to irradiation in terms of TNT induction and mitochondria transfer, although the correlation with the disease progression and therapy-resistance needs to be further addressed. Thus, TNT-based communication is active in different GSLCs derived from the external tumoral areas associated to GBM relapse, and we propose that they participate together with TMs in tumor networking.

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“…Their presence and ability to transfer cellular material including organelles, has been correlated with the induction of migratory ability, angiogenesis, cell proliferation ad therapy-resistance [14,27]. Few reports have addressed the presence of TNTs in GBM, where it was shown that GBM-derived cell lines in culture were able to form TNT-like connections [28,29,32] [13,14]. Nevertheless, the aggressiveness of GBMs has been correlated before with the establishment of tumor networking based on TMs [10].…”

Section: Discussionmentioning

confidence: 99%

“…They appear to play a critical role in several physio-pathological contexts, as in the spreading of protein aggregates in various neurodegenerative diseases [18][19][20][21][22] or in the transmission of bacteria [23] and viruses [24,25] and , possibly, during development [26]. Functional TNTs have been shown in a variety of cancers using in vitro and ex vivo models [13] where they could be exploited as route for the exchange of material between cancer cells or with the tumoral microenvironment. As consequence of this transfer, cells can acquire new abilities as enhanced metabolic plasticity, migratory phenotype, angiogenic ability and therapy-resistance.…”

Section: Introductionmentioning

confidence: 99%

Patient-derived Glioblastoma Stem cells transfer mitochondria through Tunneling Nanotubes in Tumor Organoids

Pinto

¹

,

Saenz-de-Santa-Maria

²

,

Chastagner

³

et al. 2020

Preprint

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Glioblastoma (GBM) is the most aggressive brain cancer and its relapse after surgery, chemo and radiotherapy appears to be led by GBM stem cells (GSLCs). Also, tumor networking and intercellular communication play a major role in driving GBM therapy-resistance. Tunneling Nanotubes (TNTs), thin membranous open-ended channels connecting distant cells, have been observed in several types of cancer, where they emerge to drive a more malignant phenotype. Here, we investigated whether GBM cells are capable to intercommunicate by TNTs. Two GBM stem-like cells (GSLCs) were obtained from the external and infiltrative zone of one GBM from one patient. We show, for the first time, that both GSLCs, grown in classical 2D culture and in 3D-tumor organoids, formed functional TNTs which allowed mitochondria transfer. In the organoid model, recapitulative of several tumor’s features, we observed the formation of a network between cells constituted of both Tumor Microtubes (TMs), previously observed in vivo, and TNTs. In addition, the two GSLCs exhibited different responses to irradiation in terms of TNT induction and mitochondria transfer, although the correlation with the disease progression and therapy-resistance needs to be further addressed. Thus, TNT-based communication is active in different GSLCs derived from the external tumoral areas associated to GBM relapse, and we propose that they participate together with TMs in tumor networking.

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“…Homeostatic communications between the neural cells and neurovasculature in the brain are essential for the physiological functions of the central nervous system (CNS). The efficacy of these communications depends on the integrity of neurons and glia, synapses and the nanostructures called tunneling nanotubes (TNTs) [ 7 , 8 , 9 ]. The physical characteristics of TNTs can spread over a long-range, with lengths up to 200 μm and diameters from 0.5 to 0.7 μm, depending on how these structures are defined or identified.…”

Section: Neurons and Glial Cells In The Brainmentioning

confidence: 99%

Dendrimers as Modulators of Brain Cells

Maysinger

¹

,

Zhang

²

,

Kakkar

³

2020

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Nanostructured hyperbranched macromolecules have been extensively studied at the chemical, physical and morphological levels. The cellular structural and functional complexity of neural cells and their cross-talk have made it rather difficult to evaluate dendrimer effects in a mixed population of glial cells and neurons. Thus, we are at a relatively early stage of bench-to-bedside translation, and this is due mainly to the lack of data valuable for clinical investigations. It is only recently that techniques have become available that allow for analyses of biological processes inside the living cells, at the nanoscale, in real time. This review summarizes the essential properties of neural cells and dendrimers, and provides a cross-section of biological, pre-clinical and early clinical studies, where dendrimers were used as nanocarriers. It also highlights some examples of biological studies employing dendritic polyglycerol sulfates and their effects on glia and neurons. It is the aim of this review to encourage young scientists to advance mechanistic and technological approaches in dendrimer research so that these extremely versatile and attractive nanostructures gain even greater recognition in translational medicine.

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Tunneling Nanotubes: The Fuel of Tumor Progression?

Cited by 106 publications

References 91 publications

Patient-derived glioblastoma stem cells transfer mitochondria through tunneling nanotubes in tumor organoids

Patient-derived glioblastoma stem cells transfer mitochondria through tunneling nanotubes in tumor organoids

Patient-derived Glioblastoma Stem cells transfer mitochondria through Tunneling Nanotubes in Tumor Organoids

Dendrimers as Modulators of Brain Cells

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