The Cannabinoid Receptor 2 Prevents Retinoblastoma Cell Migration

Abstract

Retinoblastoma (RB) is a rare cancer of the retina and it is the most common intraocular malignancy present in children less than 5 years of age. Current treatments cure over 95% of RB when it is restricted to the internal part of the eye, however less than 10% of children with extraocular RB survive. The endocannabinoid system has been found to be effective anti‐cancer agents in different cancer types, yet in RB the role of cannabinoid receptors or their ligands has not been elucidated. Our main objective is to determine the role of the cannabinoid 1 receptor (CB1R) and the cannabinoid 2 receptor (CB2R) in regulating RB progression with an emphasis in tumor invasion, using human RB cells and human tumors. Data from our laboratory demonstrate that in contrast to CB1R, the RNA expression of the CB2R is upregulated in RB cells and tumors. We hypothesize that the migration and invasion of highly aggressive RB cells (Y79) is modulated specifically by the CB2R. Our results show a significant upregulation in the protein expression levels of CB2Rs in RB cells and tumors when compared to fetal retina. To elucidate the migration rate, we performed wound healing assays using Y79 cells that were exposed to a synthetic agonist that activates both, CB1Rs and CB2Rs, CP55,940. Results demonstrate a time‐dependent effect in the cell's migration upon activation of the receptors. Our data suggests a functional role for CBR2 in modulating RB cell behavior. Ongoing studies using flow cytometry assay will determine the effect of CP55,940 and 2AG, a different endogenous ligand, in promoting RB cell cycle and viability. Future experiments will test the effects of CBR2 specific ligands in halting optic nerve invasion in an in vivo orthotopic RB xenograft model, hence preventing brain metastasis.Support or Funding InformationGrants: RCMI‐NIMHD 8G12MD007600 to JFO; NIH NIH‐NIDA R01 DA037924 to GY; NIGMS‐RISE program.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.