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Spontaneous involution of pediatric low-grade gliomas: high expression of cannabinoid receptor 1 (CNR1) at the time of diagnosis may indicate involvement of the endocannabinoid system

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Abstract

Background

Pediatric low-grade gliomas (P-LGG) consist of a mixed group of brain tumors that correspond to the majority of CNS tumors in children. Notably, they may exhibit spontaneous involution after subtotal surgical removal (STR). In this study, we investigated molecular indicators of spontaneous involution in P-LGG.

Methods

We performed an integrated molecular analysis including high throughput gene expression (GE), microRNA (miRNA) expression data of primary, untreated tumors from patients with P-LGG who underwent STR at our institution, with at least 10 years follow-up.

Results

We identified a set of protein-coding genes and miRNAs significantly differentially expressed in P-LGG that presented spontaneous involution (involution—I) or without progression (stable—S) after STR alone. The cannabinoid receptor 1 (CNR1 or CB1) gene (FC = 2.374; p value = 0.007) was at the top of the list and predicted to be regulated by hsa-miR-29b-3p (FC = −2.353, p value = 0.0001). CNR1 also showed a trend to be higher expressed in S/I by immunohistochemistry.

Conclusions

The P-LGG, which remained stable or that presented spontaneous involution after STR, showed significantly higher CNR1 expression at the time of diagnosis. We hypothesize that high expression levels of CNR1 provide tumor susceptibility to the antitumor effects of circulating endocannabinoids like anandamide, resulting in tumor involution. This corroborates with reports suggesting that CNR1 agonists and activators of the endocannabinoid system may represent therapeutic opportunities for children with LGG. We also suggest that CNR1 may be a prognostic marker for P-LGG. This is the first time spontaneous involution of P-LGG has been suggested to be induced by endocannabinoids.

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Acknowledgments

Funded by the Voices Against Brain Cancer Foundation (Fund#925432) and the Lurie Children’s Hospital Faculty Practice Plan Development Funding (Fund#931220).

We thank Kashyap Patel MS and Naira Margaryan DVM, Ph.D. for technical support; Aline T. Sredni and Jessica Jakubowski BS for editorial assistance.

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Authors and Affiliations

  1. Ann and Robert H. Lurie Children’s Hospital of Chicago, Division of Pediatric Neurosurgery, Hospital of Chicago, 225 E Chicago Ave., Chicago, IL, 60611, USA

    Simone Treiger Sredni, Mario Suzuki, Tatiana Pundy & Tadanori Tomita

  2. Feinberg School of Medicine, Department of Surgery, Northwestern University, 303 E Chicago Ave, Chicago, IL, 60611, USA

    Simone Treiger Sredni & Tadanori Tomita

  3. Cancer Biology and Epigenomics, Stanley Manne Children’s Research Institute, 2430 North Halsted St., Chicago, IL, 60614, USA

    Simone Treiger Sredni

  4. Joseph J. Zilber School of Public Health, University of Wisconsin, 1240 N 10th St, Milwaukee, WI, 53205, USA

    Chiang-Ching Huang

  5. Department of Neurosurgery, Juntendo University, School of Medicine, Hongo, 2-1-1 Bunkyo-ku, Tokyo, 113-8421, Japan

    Mario Suzuki

  6. Ann and Robert H. Lurie Children’s Hospital of Chicago, Department of Pathology and Laboratory Medicine, Hospital of Chicago, 225 E Chicago Ave., Chicago, IL, 60611, USA

    Pauline Chou

  7. Feinberg School of Medicine, Department of Pediatrics, Northwestern University, 303 E Chicago Ave, Chicago, IL, 60611, USA

    Pauline Chou

Authors
  1. Simone Treiger Sredni
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  2. Chiang-Ching Huang
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  3. Mario Suzuki
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  4. Tatiana Pundy
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  6. Tadanori Tomita
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Correspondence to Simone Treiger Sredni.

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Sredni, S.T., Huang, CC., Suzuki, M. et al. Spontaneous involution of pediatric low-grade gliomas: high expression of cannabinoid receptor 1 (CNR1) at the time of diagnosis may indicate involvement of the endocannabinoid system. Childs Nerv Syst 32, 2061–2067 (2016). https://doi.org/10.1007/s00381-016-3243-7

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  • DOI: https://doi.org/10.1007/s00381-016-3243-7

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