Effect of proton beam irradiation on the regulation of metastasis-enhancing factors in MCF-7 human breast cancer cells

Abstract

Metastasis is a major cause of poor prognosis and recurrence in cancer patients. We have previously reported that cancer metastasis may be prevented by proton beam irradiation via the induction of tissue inhibitor of matrix metalloproteases-1 and -2, known as anti-metastatic factors, and the suppression of aromatase in MCF-7 human breast cancer cells. However, the prior report did not show the effect of proton beam irradiation on metastasis-enhancing factors. Therefore, in this study, the effects of proton beam irradiation on the regulation of metastasis-enhancing factors, including cyclooxygenase-2 (COX-2), matrix metalloproteinase-9 (MMP-9), urokinase plasminogen activator (uPA) and uPA receptor (uPAR), were investigated in MCF-7 human breast cancer cells. 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced expression of COX-2, an important protein in metastasis and tumor growth in breast cancer, was down-regulated in a dose-dependent manner in MCF-7 human breast cancer cells irradiated by a proton beam. Proton beam irradiation also decreased MMP-9 activity and expression induced by TPA. Furthermore, proton beam irradiation dose-dependently inhibited uPA and uPA receptor (uPAR) expression. In conclusion, the present investigation demonstrated that TPA-induced metastatic activity in MCF-7 human breast cancer cells is effectively lessened by proton beam irradiation via the reversal of COX-2, MMP-9, uPA and uPAR expressions and MMP-9 activity.