Brain tumour cells interconnect to a functional and resistant network
Brain tumour cells interconnect to a functional and resistant network
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DOI：
10.1038/nature16071
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发表时间：
2015-12-03
期刊：
影响因子：
64.8
通讯作者：
Winkler, Frank
中科院分区：
文献类型：
--
作者：
Osswald, Matthias;Jung, Erik;Winkler, Frank
星形细胞脑肿瘤，包括胶质母细胞瘤，是以弥漫性浸润性生长为特征的不可治愈的肿瘤。在这里，我们表明，星形细胞瘤中的许多肿瘤细胞延伸超长膜突起，并使用这些不同的肿瘤微管作为脑侵袭，增殖和长距离互连的途径。由此产生的网络允许通过微管相关的间隙连接进行多细胞通信。当网络发生损坏时，肿瘤微管被用于修复。此外，微管连接的星形细胞瘤细胞，而不是那些在肿瘤进展过程中保持不连接的细胞，被保护免受放射治疗造成的细胞死亡。神经元生长相关蛋白43对微管的形成和功能非常重要，并驱动微管依赖性肿瘤细胞的侵袭、增殖、互连和辐射抗性。少突胶质细胞脑肿瘤缺乏这种机制。总之，星形细胞瘤可以发展功能性多细胞网络结构。通过靶向星形细胞瘤细胞的肿瘤微管来断开星形细胞瘤细胞的连接，这成为降低这种疾病的治疗抗性的新原理。
Astrocytic brain tumours, including glioblastomas, are incurable neoplasms characterized by diffusely infiltrative growth. Here we show that many tumour cells in astrocytomas extend ultra-long membrane protrusions, and use these distinct tumour microtubes as routes for brain invasion, proliferation, and to interconnect over long distances. The resulting network allows multicellular communication through microtube-associated gap junctions. When damage to the network occurred, tumour microtubes were used for repair. Moreover, the microtube-connected astrocytoma cells, but not those remaining unconnected throughout tumour progression, were protected from cell death inflicted by radiotherapy. The neuronal growth-associated protein 43 was important for microtube formation and function, and drove microtube-dependent tumour cell invasion, proliferation, interconnection, and radioresistance. Oligodendroglial brain tumours were deficient in this mechanism. In summary, astrocytomas can develop functional multicellular network structures. Disconnection of astrocytoma cells by targeting their tumour microtubes emerges as a new principle to reduce the treatment resistance of this disease.