Wykosky J et al. (2005) EphA2 as a novel molecular marker and target in glioblastoma multiforme. Mol Cancer Res 3: 541–551

Researchers in the USA recently investigated expression of the EphA2 receptor and its ligand ephrinA1 in glioblastoma multiforme (GBM) cells. EphA2 and ephrinA1 have previously been associated with the endothelial cells of tumor neovasculature, and the results of this study indicate that EphA2 could be a reliable marker of GBM.

Wykosky et al. quantified the expression of EphA2 and ephrinA1 in human GBM cells and normal brain using western blotting and immunohistochemical techniques. They found that in the vast majority of cases the level of EphA2 was much higher in GBM tumors than in normal brain tissue. By contrast, ephrinA1 was expressed at a very low level in both GBM and normal brain specimens.

By growing GBM cell lines demonstrating high levels of EphA2 expression either in the presence or absence of ephrinA1, the authors found that ephrinA1 had a dose-dependent inhibitory effect on the growth of GBM cells. The effect of exogenous ephrinA1 exposure on the invasive quality of high EphA2-expressing GBM cells was also investigated, and it was found that higher ephrinA1 concentrations were associated with a reduction in the invasiveness of GBM cells.

The authors suggest that the overexpression of EphA2 in GBM cells—possibly resulting from decreased interaction between the receptor and the inhibitory ephrinA1 in malignant cells—has importance in the oncogenic properties of GBM. They propose that the EphA2/ephrinA1 system could be a novel target for the development of molecular therapeutic interventions against GBM.