Tanaka M, Kogawa K, Nishihori Y, Kuribayashi K, Nakamura K, Muramatsu H, Koike K, Sakamaki S, Niitsu Y
Fourth Department of Internal Medicine, Sapporo Medical University School of Medicine, Japan.
Int J Cancer. 1997 Oct 9;73(2):187-92. doi: 10.1002/(sici)1097-0215(19971009)73:2<187::aid-ijc4>3.0.co;2-s.
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 mocktransfectant 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.
我们之前曾描述过铜锌超氧化物歧化酶（SOD）活性与人类舌癌细胞克隆侵袭性之间的负相关关系。在这些细胞中，通过转染反义cDNA抑制铜锌SOD活性可增强体外运动能力。本研究旨在确定细胞内铜锌SOD活性与运动能力之间的负相关关系是否为其他肿瘤细胞的普遍特性，以及该酶是否确实决定体内转移潜能。将具有低转移活性的小鼠甲基胆蒽诱导的肉瘤来源的ML-01细胞转染反义铜锌SOD cDNA。分析了两个具有非常不同SOD活性的克隆——SOD活性被抑制程度最高的ML-AS2和被抑制程度最低的ML-AS5——的运动能力和转移能力。与空载体转染的ML-neo相比，ML-AS2和ML-AS5的转移潜能和运动能力分别提高了4.5倍和2.1倍。超氧化物处理增强了反义克隆的运动能力，但未增强ML-neo细胞的运动能力。我们的结果清楚地表明，细胞内铜锌SOD水平、细胞运动能力和体内转移潜能之间存在负相关关系。
