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.
A glioblastoma stem cell (GSC) line, GSC11, grows as neurospheres in serum-free media supplemented with EGF (epidermal growth factor) and bFGF (basic fibroblast growth factor), and, if implanted in nude mice brains, will recapitulate high-grade glial tumors.
A bispecific ligand-directed toxin (BLT), called EGFATFKDEL, consisting of human epidermal growth factor, a fragment of urokinase, and truncated pseudomonas exotoxin (PE38) was assembled in order to target human glioblastoma.
Because oncogene MET and EGF receptor (EGFR) inhibitors are in clinical development against several types of cancer, including glioblastoma, it is important to identify predictive markers that indicate patient subgroups suitable for such therapies.
Here we report the development and selection for a rearranged amplified EGF receptor, which lacks cytoplasmic amino acid sequences in a human glioblastoma xenograft.
Here, we found that expression of EphA3 is up-regulated in response to epidermal growth factor (EGF) stimulation and promotes formation of cell aggregates in suspension culture of glioblastoma cells.
High-level EGFR amplification was rapidly lost in 5 glioblastoma cultures supplemented with EGF, whereas it was preserved in cultures from the same tumors established without EGF.
In addition, ectopic expression of α-catenin or depletion of β-catenin suppresses EGF-promoted glioblastoma cell migration, invasion, and proliferation.
In view of the similarity to the activated viral and cellular erbB genes in the avian system, these mutated and overexpressed EGF receptors might play a role in the onset or development of human glioblastoma cells.
Kinase-deficient erbB proteins reduced epidermal growth factor (EGF)-induced tyrosine phosphorylation of endogenous Shc proteins and also reduced immediate and sustained EGF-induced ERK MAPK activities in human glioblastoma cells, although basal ERK MAPK activities were unaffected.