Emerging intersections between neuroscience and glioma biology

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Abstract

The establishment of neuronal and glial networks in the brain depends on the activities of neural progenitors, which are influenced by cell-intrinsic mechanisms, interactions with the local microenvironment and long-range signaling. Progress in neuroscience has helped identify key factors in CNS development. In parallel, studies in recent years have increased our understanding of molecular and cellular factors in the development and growth of primary brain tumors. To thrive, glioma cells exploit pathways that are active in normal CNS progenitor cells, as well as in normal neurotransmitter signaling. Furthermore, tumor cells of incurable gliomas integrate into communicating multicellular networks, where they are interconnected through neurite-like cellular protrusions. In this Review, we discuss evidence that CNS development, organization and function share a number of common features with glioma progression and malignancy. These include mechanisms used by cells to proliferate and migrate, interact with their microenvironment and integrate into multicellular networks. The emerging intersections between the fields of neuroscience and neuro-oncology considered in this review point to new research directions and novel therapeutic opportunities.

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Fig. 1: A perivascular niche for neural and brain tumor stem-like cells.
Fig. 2: Neurotransmitter signaling in the neurogenic niche and in gliomas.
Fig. 3: Similarities between NPC migration and glioma cell invasion.
Fig. 4: Schematic summary of TM functions and molecular drivers.
Fig. 5: Multicellular networks and intercellular communication in the neurogenic niche and in brain tumors.

Change history

  • 19 November 2019

    When this article was initially published online, the Editorial Summary was missing. It should read: “Malignant gliomas recapitulate steps in neurodevelopment to form organ-like structures. Jung et al. review how neuroscience can provide novel insights into glioma biology, and how these insights might be used for future therapeutic approaches.”

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Author information

E.J., J.A., M.O., W.W., H.M., and F.W. wrote the manuscript. E.J. created the figures. J.A. acquired the immunofluorescence image of the SVZ. E.J. acquired the two-photon microscopy image of the glioma cells in vivo.

Correspondence to Frank Winkler.

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Competing interests

E.J., F.W., and W.W. report the patent (WO2017020982A1) “Agents for use in the treatment of glioma.” F.W. is co-founder of DC Europa Ltd (a company trading under the name Divide & Conquer), which is developing new medicines for the treatment of glioma. Divide & Conquer also provides research funding to F.W.’s lab under a research collaboration agreement.

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Peer review information Nature Neuroscience thanks Benjamin Deneen and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Jung, E., Alfonso, J., Osswald, M. et al. Emerging intersections between neuroscience and glioma biology. Nat Neurosci 22, 1951–1960 (2019) doi:10.1038/s41593-019-0540-y

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