Ai-17 * Robo2-slit1 Signaling Implicated in Glioma Invasion
Year: 2014
Type: article
Study design: Observational Study
Abstract: Glioblastomas (GBM) account for 54.3% of newly diagnosed glioma in the United States each year. Their rapid growth and invasion into neuronal parenchyma renders them devastating, with limited treatment options and median survival of only 12-15 months. Although there have been numerous studies of molecular aberrations in GBM, few have characterized signaling pathways specifically promoting invasion. The roundabout (Robo) family of transmembrane receptors, and their Slit protein ligands, have been demonstrated to be involved in neuronal migration and outgrowth during CNS development and have also been implicated in various cancers. We hypothesized that the Slit-Robo signaling pathway may promote GBM invasion as well. We reviewed various databases and performed IHC, PCR and Western blot of the Robo-Slit family members from GBM samples obtained from our IRB approved biorepository. Analysis of the NCI Rembrandt database indicates poorer survival among glioma patients with 2 fold or greater overexpression of the Robo2 gene (17.1 months versus 37.4 months; p = 1.42E-4). Robo-Slit signaling from distinct geographic regions of GBM tumor, identified prospectively on pre-operative MRI, and sampled using stereotactic image-guided biopsies from these preselected tumor regions, revealed significant differences in Robo-Slit levels in regions characterized by tumor invasion. Tissue samples from 6 GBM and 3 control patients, revealed a 2-5-fold increase in Robo-Slit family members in GBM by IHC, and quantitative RT-PCR and Western confirmed a 101-fold increase in Robo2 mRNA expression, as well as a 19.8 fold increase in Robo2 protein relative density in GBM (respectively) compared to normal brain parenchyma in regions of tumor invasion. Slit1 and Slit 2 also demonstrated co-localization in a majority of tumor cells. These data suggest a complex and heterogeneous tumor microenvironment and implicate Robo-Slit axis signaling in GBM invasion, making it a potentially attractive therapeutic target.
Source: Neuro-Oncology
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2316500128