Tunneling Nanotubes: A new paradigm for studying intercellular communication and therapeutics in cancer.
Tunneling Nanotubes: A new paradigm for studying intercellular communication and therapeutics in cancer.
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DOI：
10.4161/cib.20569
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发表时间：
2012-07-01
影响因子：
--
通讯作者：
Subramanian S
中科院分区：
文献类型：
--
作者：
Lou E;Fujisawa S;Barlas A;Romin Y;Manova-Todorova K;Moore MA;Subramanian S
Tunneling nanotubes是一种基于肌动蛋白的细胞质延伸物，在多种细胞类型中起细胞间通道的作用。人们对所有类型细胞中细胞间通讯模式的研究重新产生了浓厚的兴趣，特别是在癌症生物学领域。在文献中也被称为“膜纳米管”、“细胞间”或“上皮”桥”或“细胞质延伸”的Tunneling nanotubes -正在积极研究它们在促进直接细胞间通讯中的作用。直到最近，这些结构才被仔细检查为在人类癌症背景下细胞货物的直接细胞间传递的独特且先前未被识别的形式。我们最近在人类恶性胸膜间皮瘤和肺腺癌中隧道纳米管的研究表明，来自几个成熟的癌细胞系的细胞之间的细胞内容物，包括蛋白质，高尔基体囊泡和线粒体的有效转移。此外，我们提供了有效的证明，这种纳米管可以在来自人类患者的原发性恶性细胞之间形成。这是第一次，我们还证明了这些结构在人体中的体内相关性，有效地成像了患者完整实体肿瘤中的纳米管。在这里，我们提供了进一步的分析和讨论，我们的研究结果，并提供了一个前瞻性的“路线图”研究隧道纳米管在人类癌症的背景下。我们希望，进一步了解的机制，转移的方法，特别是在肿瘤间质串扰的纳米管的作用将导致识别新的选择性靶点的癌症治疗。
Tunneling nanotubes are actin-based cytoplasmic extensions that function as intercellular channels in a wide variety of cell types.There is a renewed and keen interest in the examination of modes of intercellular communication in cells of all types, especially in the field of cancer biology. Tunneling nanotubes –which in the literature have also been referred to as “membrane nanotubes,” “’intercellular’ or ‘epithelial’ bridges,” or “cytoplasmic extensions” – are under active investigation for their role in facilitating direct intercellular communication. These structures have not, until recently, been scrutinized as a unique and previously unrecognized form of direct cell-to-cell transmission of cellular cargo in the context of human cancer. Our recent study of tunneling nanotubes in human malignant pleural mesothelioma and lung adenocarcinomas demonstrated efficient transfer of cellular contents, including proteins, Golgi vesicles, and mitochondria, between cells derived from several well-established cancer cell lines. Further, we provided effective demonstration that such nanotubes can form between primary malignant cells from human patients. For the first time, we also demonstrated the in vivo relevance of these structures in humans, having effectively imaged nanotubes in intact solid tumors from patients. Here we provide further analysis and discussion on our findings, and offer a prospective ‘road map’ for studying tunneling nanotubes in the context of human cancer. We hope that further understanding of the mechanisms, methods of transfer, and particularly the role of nanotubes in tumor-stromal cross-talk will lead to identification of new selective targets for cancer therapeutics.