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TRP-ing up brain tumors

Nature Medicine volume 18, pages 1175–1176 (2012)Cite this article

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Malignant gliomas are devastating, uniformly fatal cancers for which current therapies remain palliative. A new study in mice shows that neural precursor cells, abundant in neonatal brains, release a fatty acid factor that induces glioma cell death through the activation of TRPV1 channels, prolonging survival and potentially uncovering a new treatment strategy (pages 1232–1238).

In this issue of Nature Medicine, Stock et al.4 show that NPCs in the juvenile brain use a new mechanism to fight malignant gliomas, which could be exploited to develop molecules to target this same pathway in adult brain tumors. The authors show that NPCs migrate to gliomas and suppress tumor growth by releasing fatty acid ethanolamides, called endovanilloids, with antitumor activity4. These factors showed agonistic ability on the vanilloid nociceptive receptor transient receptor potential cation channel subfamily V member 1 (TRPV1), which is highly expressed in malignant gliomas. TRPV1 stimulation on tumor cells in vitro induced cell death through the activating transcription factor 3 (ATF3)-mediated endoplasmic reticulum (ER) stress pathway (Fig. 1). Notably, Stock et al.4 were able to mimic NPC-mediated tumor suppression in adult, tumor-bearing mouse brains by systemic treatment with the synthetic vanilloid arvanil. This study4 and an earlier study5 show that TRPV1 agonists such as arvanil show preclinical efficacy against malignant gliomas, particularly glioblastomas. It is interesting that the authors find that even conditioned medium from endogenous NPCs may be cytotoxic to glioma cells, in contrast to other reports in which exogenous NPCs and other stem cells track but do not kill glioma cells6.

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Figure 1: NPCs induce glioma cell death via TRPV1 channels.

Katie Vicari

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Authors and Affiliations

  1. Shideng Bao and Jeremy N. Rich are in the Department of Stem Cell Biology and Regenerative Medicine, David L. Schonberg, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.,

    David L Schonberg, Shideng Bao & Jeremy N Rich

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  1. David L Schonberg
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  2. Shideng Bao
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Correspondence to Jeremy N Rich.

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Schonberg, D., Bao, S. & Rich, J. TRP-ing up brain tumors. Nat Med 18, 1175–1176 (2012). https://doi.org/10.1038/nm.2894

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