Tunneling nanotubes evoke pericyte/endothelial communication during normal and tumoral angiogenesis
Abstract Background Nanotubular structures, denoted tunneling nanotubes (TNTs) have been described in recent times as involved in cell-to-cell communication between distant cells. Nevertheless, TNT-like, long filopodial processes had already been described in the last century as connecting facing, g...
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BMC
2018-10-01
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Series: | Fluids and Barriers of the CNS |
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Online Access: | http://link.springer.com/article/10.1186/s12987-018-0114-5 |
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Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Mariella Errede Domenica Mangieri Giovanna Longo Francesco Girolamo Ignazio de Trizio Antonella Vimercati Gabriella Serio Karl Frei Roberto Perris Daniela Virgintino |
spellingShingle |
Mariella Errede Domenica Mangieri Giovanna Longo Francesco Girolamo Ignazio de Trizio Antonella Vimercati Gabriella Serio Karl Frei Roberto Perris Daniela Virgintino Tunneling nanotubes evoke pericyte/endothelial communication during normal and tumoral angiogenesis Fluids and Barriers of the CNS Tunneling nanotubes Pericytes Cell-to-cell communication Angiogenesis Developing cerebral cortex Glioblastoma |
author_facet |
Mariella Errede Domenica Mangieri Giovanna Longo Francesco Girolamo Ignazio de Trizio Antonella Vimercati Gabriella Serio Karl Frei Roberto Perris Daniela Virgintino |
author_sort |
Mariella Errede |
title |
Tunneling nanotubes evoke pericyte/endothelial communication during normal and tumoral angiogenesis |
title_short |
Tunneling nanotubes evoke pericyte/endothelial communication during normal and tumoral angiogenesis |
title_full |
Tunneling nanotubes evoke pericyte/endothelial communication during normal and tumoral angiogenesis |
title_fullStr |
Tunneling nanotubes evoke pericyte/endothelial communication during normal and tumoral angiogenesis |
title_full_unstemmed |
Tunneling nanotubes evoke pericyte/endothelial communication during normal and tumoral angiogenesis |
title_sort |
tunneling nanotubes evoke pericyte/endothelial communication during normal and tumoral angiogenesis |
publisher |
BMC |
series |
Fluids and Barriers of the CNS |
issn |
2045-8118 |
publishDate |
2018-10-01 |
description |
Abstract Background Nanotubular structures, denoted tunneling nanotubes (TNTs) have been described in recent times as involved in cell-to-cell communication between distant cells. Nevertheless, TNT-like, long filopodial processes had already been described in the last century as connecting facing, growing microvessels during the process of cerebral cortex vascularization and collateralization. Here we have investigated the possible presence and the cellular origin of TNTs during normal brain vascularization and also in highly vascularized brain tumors. Methods We searched for TNTs by high-resolution immunofluorescence confocal microscopy, applied to the analysis of 20-µm, thick sections from lightly fixed, unembedded samples of both developing cerebral cortex and human glioblastoma (GB), immunolabeled for endothelial, pericyte, and astrocyte markers, and vessel basal lamina molecules. Results The results revealed the existence of pericyte-derived TNTs, labeled by proteoglycan NG2/CSPG4 and CD146. In agreement with the described heterogeneity of these nanostructures, ultra-long (> 300 µm) and very thin (< 0.8 µm) TNTs were observed to bridge the gap between the wall of distant vessels, or were detected as short (< 300 µm) bridging cables connecting a vessel sprout with its facing vessel or two apposed vessel sprouts. The pericyte origin of TNTs ex vivo in fetal cortex and GB was confirmed by in vitro analysis of brain pericytes, which were able to form and remained connected by typical TNT structures. Conclusions None of the multiple roles described for TNTs can be excluded from a possible involvement during the processes of both normal and pathological vessel growth. A possible function, suggested by the pioneering studies made during cerebral cortex vascularization, is in cell searching and cell-to-cell recognition during the processes of vessel collateralization and vascular network formation. According to our results, it is definitely the pericyte-derived TNTs that seem to actively explore the surrounding microenvironment, searching for (site-to-site recognition), and connecting with (pericyte-to-pericyte and/or pericyte-to-endothelial cell communication), the targeted vessels. This idea implies that TNTs may have a primary role in the very early phases of both physiological and tumor angiogenesis in the brain. |
topic |
Tunneling nanotubes Pericytes Cell-to-cell communication Angiogenesis Developing cerebral cortex Glioblastoma |
url |
http://link.springer.com/article/10.1186/s12987-018-0114-5 |
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doaj-e341a26eb24f41f999a416bf4ee6313d2020-11-25T00:09:23ZengBMCFluids and Barriers of the CNS2045-81182018-10-0115111710.1186/s12987-018-0114-5Tunneling nanotubes evoke pericyte/endothelial communication during normal and tumoral angiogenesisMariella Errede0Domenica Mangieri1Giovanna Longo2Francesco Girolamo3Ignazio de Trizio4Antonella Vimercati5Gabriella Serio6Karl Frei7Roberto Perris8Daniela Virgintino9Department of Basic Medical Sciences, Neurosciences, and Sensory Organs, Human Anatomy and Histology Unit, University of Bari School of MedicineDepartment of Medical and Surgical Sciences, Biomedical Unit ‘E. Altomare’, University of FoggiaDepartment of Basic Medical Sciences, Neurosciences, and Sensory Organs, Molecular Biology Laboratory, University of Bari School of MedicineDepartment of Basic Medical Sciences, Neurosciences, and Sensory Organs, Human Anatomy and Histology Unit, University of Bari School of MedicineDepartment of Basic Medical Sciences, Neurosciences, and Sensory Organs, Human Anatomy and Histology Unit, University of Bari School of MedicineDepartment of Biomedical Sciences and Human Oncology, University of Bari School of MedicineDepartment of Emergency and Organ Transplantation, Division of Pathology, University of Bari School of MedicineDepartment of Neurosurgery, University Hospital ZurichCOMT-Centre for Molecular and Translational Oncology & Department of Chemical and Life Sciences and Environmental Sustainability, University of ParmaDepartment of Basic Medical Sciences, Neurosciences, and Sensory Organs, Human Anatomy and Histology Unit, University of Bari School of MedicineAbstract Background Nanotubular structures, denoted tunneling nanotubes (TNTs) have been described in recent times as involved in cell-to-cell communication between distant cells. Nevertheless, TNT-like, long filopodial processes had already been described in the last century as connecting facing, growing microvessels during the process of cerebral cortex vascularization and collateralization. Here we have investigated the possible presence and the cellular origin of TNTs during normal brain vascularization and also in highly vascularized brain tumors. Methods We searched for TNTs by high-resolution immunofluorescence confocal microscopy, applied to the analysis of 20-µm, thick sections from lightly fixed, unembedded samples of both developing cerebral cortex and human glioblastoma (GB), immunolabeled for endothelial, pericyte, and astrocyte markers, and vessel basal lamina molecules. Results The results revealed the existence of pericyte-derived TNTs, labeled by proteoglycan NG2/CSPG4 and CD146. In agreement with the described heterogeneity of these nanostructures, ultra-long (> 300 µm) and very thin (< 0.8 µm) TNTs were observed to bridge the gap between the wall of distant vessels, or were detected as short (< 300 µm) bridging cables connecting a vessel sprout with its facing vessel or two apposed vessel sprouts. The pericyte origin of TNTs ex vivo in fetal cortex and GB was confirmed by in vitro analysis of brain pericytes, which were able to form and remained connected by typical TNT structures. Conclusions None of the multiple roles described for TNTs can be excluded from a possible involvement during the processes of both normal and pathological vessel growth. A possible function, suggested by the pioneering studies made during cerebral cortex vascularization, is in cell searching and cell-to-cell recognition during the processes of vessel collateralization and vascular network formation. According to our results, it is definitely the pericyte-derived TNTs that seem to actively explore the surrounding microenvironment, searching for (site-to-site recognition), and connecting with (pericyte-to-pericyte and/or pericyte-to-endothelial cell communication), the targeted vessels. This idea implies that TNTs may have a primary role in the very early phases of both physiological and tumor angiogenesis in the brain.http://link.springer.com/article/10.1186/s12987-018-0114-5Tunneling nanotubesPericytesCell-to-cell communicationAngiogenesisDeveloping cerebral cortexGlioblastoma |