Introduction: Glioblastoma (GBM) is the most common and lethal form of primary brain tumor. Studies have shown that intracranial dissemination is associated with decreased overall survival, however the mechanisms underlying invasion are not fully understood. Recent reports have shown that EGF module-containing mucin-like receptor 2, a receptor expressed mainly on the surface of leukocytes, is expressed in GBM and confers a poor prognosis and increased invasive potential in vitro.

Methods: Using previously established culturing conditions, we isolated patient-matched cultures of primary glioblastoma and brain tumor initiating cells, defined by their expression of the stem cell markers nestin and SOX-2 as well as the ability to form neurospheres. RNA and protein were isolated from these cells and used for PCR and Western blot analysis.

Results: Primary GBM cells were found to express increased levels of EMR2 compared to patient-matched brain tumor initiating cells. Both groups of cells demonstrated varying levels of EMR2 isoform expression, with more differentiated GBM generally expressing higher levels. PCR using probes spanning the variably spliced regions of the gene confirmed the presence of isoforms at the transcript level.

Conclusions: Our data demonstrates increased expressed of EMR2 in differentiated GBM compared to the less differentiated brain tumor initiating cells. Given its role in leukocyte adhesion and migration, as well as invasive properties in vitro, EMR2 likely confers a more invasive phenotype in GBM. Data from The Cancer Genome Atlas has demonstrated poor survival in tumors with upregulation of EMR2, suggesting that this marker may aid in the classification of GBM or serve as an attractive therapeutic target. The functional significance of EMR2 and its isoforms is not fully understood, however its close family member CD97 is known to exhibit isoform-dependent phenotypes, with certain variants associated with increased invasive potential. Further studies are needed to fully understand this protein’s role in GBM invasion.

Patient Care: Contribute to the potential identification of new therapeutic targets for glioblastoma

Learning Objectives: 1. Understand the importance of invasion in glioblastoma 2. Recognize the potential role of EMR2 in glioblastoma invasion.

References: Rutkowski, M. et al. Epidermal growth factor module-containing mucin-like receptor 2 is a newly identified adhesion G protein-coupled receptor associated with poor overall survival and an invasive phenotype in glioblastoma. J. Neuro-oncol. 2001;105:165-71