RADIATION-INDUCED INCREASE IN EXPRESSION OF THE ALPHA(IIB)BETA(3) INTEGRIN IN MELANOMA-CELLS - EFFECTS ON METASTATIC POTENTIAL

We investigated the effects of nonlethal γ radiation on the metastatic potential of the murine tumor cell line, B16 melanoma. The ability of B16 cells to adhere to fibronectin, which is in part mediated by the α(IIb)β3 integrin receptor, is predictive of metastatic potential. We determined that exposure to 0.25-2.5 Gy γ radiation significantly enhanced B16 cell adhesion to fibronectin. The radiation-enhanced adhesion was dependent on enhanced expression of the α(IIb)β3 integrin. We observed that 15 min after 0.5 Gy radiation, 99% of irradiated B16 tumor cells were positively labeled with monoclonal antibodies directed against α(IIb)β3 compared to 22% of sham- irradiated cells. Radiation-enhanced expression of the α(IIb)β3 receptor is reversible and down-regulation begins within 2-4 h postirradiation. Finally, we found that irradiation significantly enhanced the ability of B16 cells to form metastases in a lung colony assay. It is concluded that a relationship exists between radiation effects on the B16 tumor cells, α(IIb)β3 receptor expression, adhesion in vitro, and metastasis in vivo. We suggest that low-dose radiation, at levels comparable to those used in fractionated or hyperfractionated radiotherapy, may alter the metastatic phenotype and potential of surviving tumor cells via a rapid alteration in their surface expression of α(IIb)β3 integrin receptors.