We investigated the presence of EphA2, and its ligand, ephrinA1, in glioblastoma 
multiforme (GBM), a malignant neoplasm of glial cells, and normal brain. We also 
initially examined the functional importance of the interaction between EphA2 
and ephrinA1 in glioma cells. Expression and localization of EphA2 and ephrinA1 
in human GBM and normal brain were examined using Western blotting, 
immunofluorescence, and immunohistochemistry. A functional role for EphA2 was 
investigated by assessing the activation status of the receptor and the effect 
of ephrinA1 on the anchorage-independent growth and invasiveness of GBM cells. 
We found EphA2 to be elevated in approximately 90% of GBM specimens and cell 
lines but not in normal brain, whereas ephrinA1 was present at consistently low 
levels in both GBM and normal brain. EphA2 was activated and phosphorylated by 
ephrinA1 in GBM cells. Furthermore, ephrinA1 induced a prominent, dose-dependent 
inhibitory effect on the anchorage-independent growth and invasiveness of GBM 
cells highly overexpressing EphA2, which was not seen in cells expressing low 
levels of the receptor. Thus, EphA2 is both specifically overexpressed in GBM 
and expressed differentially with respect to its ligand, ephrinA1, which may 
reflect on the oncogenic processes of malignant glioma cells. EphA2 seems to be 
functionally important in GBM cells and thus may play an important role in GBM 
pathogenesis. Hence, EphA2 represents a new marker and novel target for the 
development of molecular therapeutics against GBM.