Influence of Eph receptors on melanoma cell properties after X-ray irradiation

X-ray irradiation has an influence on metastatic properties of tumor cells. Moreover, metastasis and cellular motility can be modified by EphA2 and EphA3, two members of the Eph receptor/ephrin family of receptor tyrosine kinases. However, a link between X-ray irradiation, Eph receptor expression, and modification of metastasis-relevant cellular properties has not yet been shown.
In this study, we irradiated one pre-metastatic and three metastatic human melanoma cells lines with X-rays and found impairment of cell growth and clonal growth. Regarding adhesion, an irradiation-induced increase paralleled by a decrease in migration was detected in Mel-Juso and Mel-Juso-L3 cells and, in part, also in A375 cells. These results indicate irradiation-induced anti-metastatic effects.
For EphA2 a decrease both in expression and activity at 7 days after irradiation was detected. In contrast, EphA3 was found to be up-regulated in 3 of 4 analyzed cell lines. Analyzing downstream signaling after irradiation decreased Src kinase phosphorylation, but unchanged focal adhesion kinase (FAK) phosphorylation was demonstrated. Our findings indicate that irradiation-induced downregulation of EphA2 and up-regulation of EphA3 in human melanoma cells is associated with anti-metastatic effects. The observed effects are assumed partly to be mediated by regulation of Src and FAK through EphA2.