Brain tumour cells interconnect to a functional and resistant network

By Matthias Osswald, E. Jung, F. Sahm, G. Solecki, V. Venkataramani, J. Blaes, S. Weil, H. Horstmann, B. Wiestler, M. Syed and 30 more. Nature, 2015

982 citations recorded by the source corpus.

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.

Subfields: Developmental Neuroscience, Genetics, Neurology

View Paper: https://www.semanticscholar.org/paper/1f5f31966d9e4b6e6feda47e5b900146aaf12ddd

How researchers see this paper

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In Developmental Neuroscience

1. Michelle Monje
2. R. Malenka
3. Fred H. Gage

In Genetics

1. Aviv Regev
2. J. Joyce
3. R. Malenka
4. D. Quail

In Neurology

1. Michelle Monje
2. J. Joyce
3. R. Malenka
4. D. Quail
5. D. Bergles
6. Gina G. Turrigiano

Citations in the corpus

• The microenvironmental landscape of brain tumors (2017, background): “Similarly, we expect that major insights will come from a detailed comparison of how distinct molecular subtypes or genetic drivers in cancer cells may differentially sculpt their microenvironment during the course of cancer progression, as already indicated from several studies discussed herein (Mi”
• Electrical and synaptic integration of glioma into neural circuits (2019, positive): “Gap junctions couple adult glioma cells through long processes called tumor microtubes 19 , which we demonstrated in primary pediatric glioma tissue (Extended Data Fig.”