De novo expression of EphA2 in osteosarcoma modulates activation of the mitogenic signalling pathway

摘要: Aims: In osteosarcoma patients the development of metastases, often to lungs, is most frequent cause death. The aim this study was elucidate molecular mechanisms governing and dissemination and, thereby, identify possible novel drug targets for improved treatment. Methods results:  Osteosarcoma samples were characterized using genome-wide microarrays: increased expression EphA2 receptor its ligand EFNA1 detected. In addition, EFNB1, EFNB3 EphA3 suggested. Immunohistochemistry revealed an absence in normal bone, de novo osteosarcomas. expressed but significantly elevated tumours. Further vitro investigations on functional role showed that binding induced tyrosine phoshorylation, degradation downstream mitogen-activated protein kinase (MAPK) activation. Interference with MAPK pathway unravelled a potential autoregulatory loop mainly via same pathway. Conclusion:  Upregulation ephrins osteosarcomas are involved oncogenic signalling thus might stimulate metastasis.