Ephrin A5 expression promotes invasion and transformation of murine fibroblasts.

Emerging evidence suggests involvement of the ephrin/Eph receptor system in tumourigenesis. Research on this new role has centred on the contribution of Eph receptors. In contrast, we focused on the elucidation of the role of ephrins, specifically ephrin A5. Results indicated an increase in invasive potential of ephrin A5-expressing murine fibroblasts, which was abolished by addition of a Src family kinase inhibitor. Furthermore, anchorage-independent growth was increased in ephrin A5-expressing cells. Stimulation with EphA5-Fc receptor increased colony size, but not colony number in ephrin A5 transfectants. Moreover, we observed morphogenetic transformation of ephrin A5-expressing 3T3 cells into a branching network when plated onto Matrigel. This behaviour was specific to ephrin A5 transfectants, as 3T3 cells expressing ephrin B1 displayed a phenotype similar to control 3T3 cells. We conclude that ectopic expression of ephrin A5 in murine fibroblasts elevates oncogenic potential, including increased invasive behaviour, anchorage-independent growth, and morphological transformation.