Suppression of intracellular Cu‐Zn SOD results in enhanced motility and metastasis of Meth A sarcoma cells

We have previously described an inverse relationship between Cu‐Zn superoxide dismutase (SOD) activity and invasiveness of a clone of human tongue cancer cells. In these cells, suppression of Cu‐Zn SOD activity by transfection with anti‐sense cDNA enhanced motility in vitro. The present studies were undertaken to determine whether the inverse relationship between intracellular Cu‐Zn SOD activity and motility is a general property of other tumor cells and whether this enzyme indeed defines in vivo metastatic potential. Murine Meth A sarcoma‐derived ML‐01 cells, which have low metastatic activity, were transfected with anti‐sense Cu‐Zn SOD cDNA. Two clones with very different SOD activities—ML‐AS2, with the most suppressed, and ML‐AS5, with the least suppressed activity—were analyzed for their motility and metastatic capability. Compared to the mock‐transfectant ML‐neo, the metastatic potential and motility of the ML‐AS2 and ML‐AS5 were increased 4.5‐ and 2.1‐fold, respectively. Superoxide treatment enhanced the motility of the AS clones but not that of the ML‐neo cells. Our results clearly show that there is an inverse relationship between the intracellular level of Cu‐Zn SOD, cell motility and in vivo metastatic potential. Int. J. Cancer 73:187–192, 1997. © 1997 Wiley‐Liss, Inc.