Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0017636 (glioblastoma)
 18,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Epidermal growth factor (EGF) module-containing mucin-like receptor 2 (EMR2) is a member of the seven span transmembrane (TM7) adhesion G-protein coupled receptor subclass. It is abundantly expressed in immune cells of myeloid origin and appears to mediate cellular adhesion, migration, and signaling. Based on an analysis showing earlier mortality among glioblastoma patients whose tumors highly express EMR2, we studied its expression patterns in glioblastoma and potential to mediate cellular proliferation and invasion. We performed univariate analysis of overall survival in GBM patients expressing low, moderate, and high amounts of EMR2 based on publicly available microarray data in the Cancer Genome Atlas (TCGA). Using RT-PCR and western blotting, we studied mRNA and protein expression patterns of EMR2, respectively. We then employed siRNA knockdown of EMR2 in two human glioblastoma cell lines expressing high levels of EMR2 to assess functional effects on cellular proliferation and invasion, in vitro. Kaplan-Meier analysis of TCGA survival data for GBM demonstrated that EMR2 levels are inversely correlated with overall time until mortality (log rank, P < 0.01). EMR2 mRNA and protein is variably expressed in primary glioblastoma samples and human glioblastoma cell lines. When comparing cells transfected with siRNA targeting EMR2 to those transfected with a negative, scramble control, there was no difference in proliferation over 72 h in the SF767 and G55 glioblastoma cell lines. However, EMR2 knockout cells demonstrated an almost 3-fold reduction in migration compared to their negative controls (P < 0.05) in the SF767 cell line, and an almost 2-fold reduction (P < 0.05) in migration in the G55 cell line. We provide evidence that EMR2 is expressed in glioblastoma and has significant functional consequences on cellular invasion, but not proliferation. In light of its ability to promote adhesion and migration in immune cells, our data suggest that EMR2 may mediate similar phenomena in glioblastoma. The invasive phenotype conferred by EMR2 correlates with clinical data demonstrating poor survival in glioblastoma patients who express high levels of EMR2 in their tumor.
 ...
PMID: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. 2150 28

Epidermal growth factor (EGF) module-containing mucin-like receptor 2 (EMR2) is a member of the seven span transmembrane adhesion G-protein coupled receptor subclass. This protein is expressed in a subset of glioblastoma (GBM) cells and associated with an invasive phenotype. The expression pattern and functional significance of EMR2 in low grade or anaplastic astrocytomas is unknown and our goal was to expand and further define EMR2's role in gliomas with an aggressive invasive phenotype. Using the TCGA survival data we describe EMR2 expression patterns across histologic grades of gliomas and demonstrate an association between increased EMR2 expression and poor survival (p < 0.05). This data supports prior functional data depicting that EMR2-positive neoplasms possess a greater capacity for infiltrative and metastatic spread. Genomic analysis suggests that EMR2 overexpression is associated with the mesenchymal GBM subtype (p < 0.0001). We also demonstrate that immunohistorchemistry is a feasible method for screening GBM patients for EMR2 expression. Protein and mRNA analysis demonstrated variable expression of all isoforms of EMR2 in all glioma grades, however GBM displayed the most diverse isoforms expression pattern as well as the highest expression of the EGF1-5 isoform of EMR2. Finally, a correlation of an increased EMR2 expression after bevacizumab treatment in glioma cells lines is identified. This observation should serve as the impetus for future studies to determine if this up-regulation of EMR2 plays a role in the observation of the diffuse and increasingly invasive recurrence patterns witnessed in a subset of GBM patients after bevacizumab treatment.
 ...
PMID:Epidermal growth factor-like module containing mucin-like hormone receptor 2 expression in gliomas. 2520 Aug 31