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. 2015 Dec 3;528(7580):93-8.
doi: 10.1038/nature16071. Epub 2015 Nov 4.

Brain tumour cells interconnect to a functional and resistant network

Matthias Osswald  1   2 , Erik Jung  1   2 , Felix Sahm  3   4 , Gergely Solecki  1   2 , Varun Venkataramani  5 , Jonas Blaes  1   2 , Sophie Weil  1   2 , Heinz Horstmann  5 , Benedikt Wiestler  1   2   6 , Mustafa Syed  1   2 , Lulu Huang  1   2 , Miriam Ratliff  2   7 , Kianush Karimian Jazi  1   2 , Felix T Kurz  8 , Torsten Schmenger  1   2 , Dieter Lemke  1   2 , Miriam Gömmel  1   2 , Martin Pauli  9 , Yunxiang Liao  1   2 , Peter Häring  10 , Stefan Pusch  3   4 , Verena Herl  11 , Christian Steinhäuser  11 , Damir Krunic  12 , Mostafa Jarahian  13 , Hrvoje Miletic  14 , Anna S Berghoff  15 , Oliver Griesbeck  16 , Georgios Kalamakis  17 , Olga Garaschuk  17 , Matthias Preusser  18 , Samuel Weiss  19   20   21 , Haikun Liu  22 , Sabine Heiland  8 , Michael Platten  1   23 , Peter E Huber  24   25 , Thomas Kuner  5 , Andreas von Deimling  3   4 , Wolfgang Wick  1   2 , Frank Winkler  1   2
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Brain tumour cells interconnect to a functional and resistant network

Matthias Osswald et al. Nature. .

Abstract

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.

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