gms | German Medical Science

Several receptor tyrosine kinases (RTK) and their ligands have been implicated in glioma biology. Recently members of the Eph-group of RTKs (Ephs) and their ligands, the ephrins, initially identified by their involvement in the cell contact-dependent regulation of CNS develoment and vascular development have been implicated in tumor biology. However, the role of Ephs and ephrins for tumor biology in general and for glioma biology in particular remains vague.

To address the role of Ephs and ephrins in glioma biology we analyzed Eph and ephrin expression in human glioma cell lines, xenografted human gliomas as well as human surgical specimens including normal brain (n=3), astrocytoma II (n=6), glioblastoma multiforme (n=26) by means of cDNA-array analysis, RT-PCR and in-situ hybridization.

c-DNA-array analysis revealed that expression of Ephs in human glioma cell lines increased after xenotransplantation into nude mice. Species specific RT-PCR on xenotransplanted gliomas revealed that Ephs and ephrins were expressed by both endothelial cells and tumor cells. To further assess the relevance of Eph/ephrin expression in human glioma, we first compared Eph/ephrin expression of astrocytoma II, glioblastoma multiforme and normal brain by RT-PCR which identified EphB4, ephrin-B2 and ephrin-B1 as the molecules with the most prominently altered expression patterns. More insight into the expression pattern of these molecules was gained by in-situ hybridization which revealed increased EphB4 and ephrin-B2 mRNA expression at sites of tumor neovascularization, while ephrin-B1 mRNA was increasingly expressed by perivascular cells.

Based on our results we propose a functional interplay between Eph/ephrin-family members during tumor progression and angiogenesis of glial brain tumors. Thus, ephs and ephrins may represent novel targets for anti-glioma therapy.