Review Article | Published:

Twisted tango: brain tumor neurovascular interactions

Nature Neuroscience volume 14, pages 13751381 (2011) | Download Citation

Abstract

The brain is a complicated organ with complexity derived from cellular and microenvironmental interactions. Similarly, brain tumor cells actively modify and are regulated by their microenvironment. Brain tumors are highly heterogeneous and frequently show a cellular hierarchy with self-renewing tumorigenic brain tumor stem cells (BTSCs) at the apex. Although BTSCs are distinct from neural stem cells, they share characteristics, including bidirectional interplay with supportive vasculature critical for maintenance of undifferentiated states and survival. BTSCs stimulate angiogenesis through growth factor secretion and are enriched in perivascular niches. Microenvironmental conditions, including hypoxia, drive expression of stem cell genes and proangiogenic factors, further linking cellular hierarchy regulation and instructive stromal elements. BTSCs may also directly contribute to tumor vasculature through plasticity toward an endothelial lineage. Interrogating the codependence of BTSCs and the perivascular niche may directly inform clinical approaches for brain tumor therapy through targeting of highly angiogenic and tumorigenic cellular subsets.

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Acknowledgements

We thank the sources of our funding, including the US National Institutes of Health (CA151522 for A.B.H.; CA142159 for J.D.L.; CA129958, CA116659 and CA154130 for J.N.R.), the American Brain Tumor Association (J.D.L.) and the James S. McDonnell Foundation (J.N.R.).

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Affiliations

  1. Department of Stem Cell Biology and Regenerative Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.

    • Anita B Hjelmeland
    • , Justin D Lathia
    •  & Jeremy N Rich
  2. Department of Medicine, Faculty of Medicine at Siriraj Hospital, Mahidol University, Bangkok, Thailand.

    • Sith Sathornsumetee
  3. Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine, Case Western Reserve University School of Medicine and University Hospitals, Cleveland, Ohio, USA.

    • Jeremy N Rich

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The authors declare no competing financial interests.

Corresponding authors

Correspondence to Anita B Hjelmeland or Jeremy N Rich.

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https://doi.org/10.1038/nn.2955

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