Publikationsrepositorium - Helmholtz-Zentrum Dresden-Rossendorf

X-ray irradiation has an influence on survival and metastatic properties of tumor cells. In turn, metastasis and cellular motility can be modified by EphA2 and EphA3, two members of the Eph receptor/ephrin family of receptor tyrosine kinases. However, links between irradiation, Eph receptor expression and modification of metastasis-relevant cellular properties have not yet been shown. In this study, we irradiated one pre-metastatic and three metastatic human melanoma cells lines, including one self-generated metastatic cell line with X-rays. At day 1 and day 7 post irradiation we analyzed cellular viability, proliferation, motility, adhesion, migration, and clonal growth. Additionally, selected Eph receptors and ephrin ligands were analyzed regarding radiationdependent changes in mRNA and protein content.

In all cell lines a dose-dependent decrease in viability and cell growth for up to 1 week after irradiation was demonstrated. Motility was decreased 1 day after treatment but showed recurrence at 7 days after X-ray. In adhesion to fibronectin, we detected an irradiation-induced increase with similar decrease in migration and clonal growth. Thus, we assume that X-ray acts merely antimetastatic on the investigated melanoma cells. For EphA2 we detected an increase in mRNA in 2 of 3 metastatic cell lines, with simultaneously decreased protein level. EphA3 was found to be upregulated in mRNA and protein in 3 of 4 cell lines. Expression of ephrinA1 and A5 was generally low and seemed unaffected by irradiation.
In conclusion, our data indicate irradiation-induced downregulation of EphA2 and up-regulation of EphA3 in human melanoma cells, leading to anti-metastatic effects such as decreased motility and migration and increased adhesion to fibronectin. Ongoing studies will further clarify underlying mechanisms and the importance of EphA2 and EphA3 in melanoma metastasis.