Tumor exosomes induce tunneling nanotubes in lipid raft-enriched regions of human mesothelioma cells.
Tumor exosomes induce tunneling nanotubes in lipid raft-enriched regions of human mesothelioma cells.
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DOI：
10.1016/j.yexcr.2014.01.014
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发表时间：
2014-04-15
影响因子：
3.7
通讯作者：
Lou E
中科院分区：
文献类型：
--
作者：
Thayanithy V;Babatunde V;Dickson EL;Wong P;Oh S;Ke X;Barlas A;Fujisawa S;Romin Y;Moreira AL;Downey RJ;Steer CJ;Subramanian S;Manova-Todorova K;Moore MAS;Lou E
Tunnel nanotubes（TnTs）是长的、非粘附的、基于肌动蛋白的细胞延伸物，其充当用于在连接的细胞之间运输细胞货物的管道。纳米管形成的机制以及肿瘤微环境和细胞信号对TnT形成的影响尚不清楚。在本研究中，我们探讨了外泌体作为间皮瘤中TnT形成的潜在介质以及脂筏与TnT形成的潜在关系。在24-48小时内，与外源性间皮瘤来源的外来体共培养的间皮瘤细胞比在没有外来体的情况下培养的细胞形成更多的TnT;并且这种作用在支持TnT形成的培养基条件（低血清、高血糖培养基）中最突出（1.3-1.9倍差异）。荧光和电子显微镜证实了分离的外泌体的纯度，并揭示了它们除了细胞外环境之外，主要定位在TnTs的基部和内部。延时显微成像显示TnTs摄取肿瘤外泌体，这促进了这些外泌体在连接细胞之间的细胞间转移。与未通过TnTs连接的细胞相比，通过TnTs连接的间皮瘤细胞也显著富集脂筏，其数量高出近2倍。我们的研究结果提供了外来体作为TnT形成的潜在趋化刺激的支持性证据，并且脂筏形成作为TnT形成细胞的潜在生物标志物。
Tunneling nanotubes (TnTs) are long, non-adherent, actin-based cellular extensions that act as conduits for transport of cellular cargo between connected cells. The mechanisms of nanotube formation and the effects of the tumor microenvironment and cellular signals on TnT formation are unknown. In the present study, we explored exosomes as potential mediators of TnT formation in mesothelioma and the potential relationship of lipid rafts to TnT formation. Mesothelioma cells co-cultured with exogenous mesothelioma-derived exosomes formed more TnTs than cells cultured without exosomes within 24-48 hours; and this effect was most prominent in media conditions (low-serum, hyperglycemic medium) that support TnT formation (1.3-1.9-fold difference). Fluorescence and electron microscopy confirmed the purity of isolated exosomes and revealed that they localized predominantly at the base of and within TnTs, in addition to the extracellular environment. Time-lapse microscopic imaging demonstrated uptake of tumor exosomes by TnTs, which facilitated intercellular transfer of these exosomes between connected cells. Mesothelioma cells connected via TnTs were also significantly enriched for lipid rafts at nearly a 2-fold higher number compared with cells not connected by TnTs. Our findings provide supportive evidence of exosomes as potential chemotactic stimuli for TnT formation, and also lipid raft formation as a potential biomarker for TnT-forming cells.
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影响因子：
9.8
作者：
Mineo, Marco;Garfield, Susan H.;Taverna, Simona;Flugy, Anna;De Leo, Giacomo;Alessandro, Riccardo;Kohn, Elise C.
通讯作者：
Kohn, Elise C.
影响因子：
--
作者：
Lou E;Fujisawa S;Barlas A;Romin Y;Manova-Todorova K;Moore MA;Subramanian S
通讯作者：
Subramanian S
影响因子：
3.7
作者：
Lou E;Fujisawa S;Morozov A;Barlas A;Romin Y;Dogan Y;Gholami S;Moreira AL;Manova-Todorova K;Moore MA
通讯作者：
Moore MA
影响因子：
20.3
作者：
de Gassart, A;Géminard, C;Vidal, M
通讯作者：
Vidal, M
影响因子：
6
作者：
Hegmans, JPJJ;Bard, MPL;Lambrecht, BN
通讯作者：
Lambrecht, BN