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
- 424 Downloads
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.
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.
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.
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.
KeywordsCB1 miR-29b Anandamide Prognosis Brain neoplasm Children
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.
Compliance with ethical standards
Conflicts of interest
The authors declare no conflicts of interest.
- 3.von Hornstein S, Kortmann RD, Pietsch T, Emser A, Warmuth-Metz M, Soerensen N, Straeter R, Graf N, Thieme B, Gnekow AK (2011) Impact of chemotherapy on disseminated low-grade glioma in children and adolescents: report from the HIT-LGG 1996 trial. Pediatr Blood Cancer 56:1046–1054CrossRefGoogle Scholar
- 6.Pisanti S, Picardi P, Pallottini V, Martini C, Petrosino S, Proto MC, Vitale M, Laezza C, Gazzerro P, Di Marzo V, Bifulco M (2015) Anandamide drives cell cycle progression through CB1 receptors in a rat model of synchronized liver regeneration. J Cell Physiol 230:2905–2914CrossRefPubMedGoogle Scholar