Lou Emil, Fujisawa Sho, Barlas Afsar, Romin Yevgeniy, Manova-Todorova Katia, Moore Malcolm A S, Subramanian Subbaya
Division of Hematology; Oncology and Transplantation; University of Minnesota; Minneapolis, MN USA.
Commun Integr Biol. 2012 Jul 1;5(4):399-403. doi: 10.4161/cib.20569.
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.
隧道纳米管是基于肌动蛋白的细胞质延伸物，在多种细胞类型中作为细胞间通道发挥作用。对所有类型细胞间通讯方式的研究重新引发了浓厚兴趣，尤其是在癌症生物学领域。隧道纳米管——在文献中也被称为“膜纳米管”“细胞间”或“上皮”桥或“细胞质延伸物”——因其在促进直接细胞间通讯中的作用而受到积极研究。直到最近，在人类癌症背景下，这些结构尚未被细究为一种独特的、先前未被认识的细胞货物直接细胞间传递形式。我们最近对人类恶性胸膜间皮瘤和肺腺癌中隧道纳米管的研究表明，在源自几种成熟癌细胞系的细胞之间，包括蛋白质、高尔基体囊泡和线粒体在内的细胞内容物能有效转移。此外，我们有效证明了此类纳米管可在人类患者的原发性恶性细胞之间形成。我们还首次证明了这些结构在人体中的体内相关性，已在患者完整实体瘤中对纳米管进行了有效成像。在此，我们对我们的发现进行进一步分析和讨论，并提供一份在人类癌症背景下研究隧道纳米管的前瞻性“路线图”。我们希望对其机制、转移方法，尤其是纳米管在肿瘤-基质相互作用中的作用有更深入的了解，将有助于识别癌症治疗的新选择性靶点。
