Tunneling nanotubes evoke pericyte/endothelial communication during normal and tumoral angiogenesis.
Tunneling nanotubes evoke pericyte/endothelial communication during normal and tumoral angiogenesis.
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DOI：
10.1186/s12987-018-0114-5
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发表时间：
2018-10-05
影响因子：
7.3
通讯作者：
Virgintino D
中科院分区：
文献类型：
--
作者：
Errede M;Mangieri D;Longo G;Girolamo F;de Trizio I;Vimercati A;Serio G;Frei K;Perris R;Virgintino D
近年来，被称为隧道纳米管(TNTs)的纳米管结构被描述为涉及远距离细胞之间的细胞间通信。然而，在上个世纪，TNT样的长丝状突起已经被描述为在大脑皮层血管化和侧化过程中连接面对、生长的微血管。在这里，我们研究了TNTs在正常脑血管形成过程中以及在高度血管化的脑肿瘤中的可能存在和细胞来源。我们通过高分辨率免疫荧光共聚焦显微镜寻找TNTs，应用于分析20微米厚的切片，切片来自发育中的大脑皮层和人脑胶质母细胞瘤(GB)的轻度固定、未包埋的样本，免疫标记内皮细胞、周细胞和星形胶质细胞标志物，以及血管基板分子。结果表明，周细胞来源的TNTs的存在，由蛋白多糖NG2/CSPG4和CD146标记。与所描述的这些纳米结构的异质性一致，观察到超长(>； 300µm)和超薄(<； 0.8µm)TNTs用于连接远处血管壁之间的间隙，或者被检测为连接一个导管萌芽与其面对的导管或两个相对的导管萌芽的短(<； 300µm)桥接电缆。通过对脑周细胞的体外分析，证实了TNTs在胎脑皮质和大脑中的周细胞起源，这些细胞能够形成并保持由典型的TNT结构连接。在正常和病理性血管生长过程中，所描述的TNTs的多种作用都不能被排除在外。在大脑皮层血管化过程中的开创性研究表明，在血管侧化和血管网络形成的过程中，细胞搜索和细胞间识别可能是一种功能。根据我们的结果，似乎是周细胞来源的TNTs似乎积极探索周围的微环境，寻找(点对点识别)，并与(周细胞到周细胞和/或周细胞到内皮细胞通讯)的靶血管连接。这一观点表明，TNTs可能在脑内生理和肿瘤血管生成的非常早期阶段发挥主要作用。本文的在线版本(10.1186/s12987-0180114-5)包含向授权用户提供的补充材料。
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. 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. 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. 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. The online version of this article (10.1186/s12987-018-0114-5) contains supplementary material, which is available to authorized users.
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影响因子：
--
作者：
Loibl M;Binder A;Herrmann M;Duttenhoefer F;Richards RG;Nerlich M;Alini M;Verrier S
通讯作者：
Verrier S
影响因子：
--
作者：
Austefjord MW;Gerdes HH;Wang X
通讯作者：
Wang X
影响因子：
11.2
作者：
Bagley, RG;Weber, W;Teicher, BA
通讯作者：
Teicher, BA
影响因子：
20.1
作者：
Climent, Montserrat;Quintavalle, Manuela;Elia, Leonardo
通讯作者：
Elia, Leonardo
影响因子：
6
作者：
Bourdeau, A;Cymerman, U;Letarte, M
通讯作者：
Letarte, M