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 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.
Tanaka
M
M
Fourth Department of Internal Medicine, Sapporo Medical University School of Medicine, Japan. niitsu@sapmed.ac.jp
Kogawa
K
K
Nishihori
Y
Y
Kuribayashi
K
K
Nakamura
K
K
Muramatsu
H
H
Koike
K
K
Sakamaki
S
S
Niitsu
Y
Y
D000818:Animals; D002448:Cell Adhesion; D002465:Cell Movement / Q000187:drug effects; D017364:Collagenases / Q000378:metabolism; D016373:DNA, Antisense / Q000494:pharmacology; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D018093:Gelatinases / Q000378:metabolism; D008175:Lung Neoplasms / Q000201:enzymology / Q000473:pathology / Q000556:secondary*; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D008666:Metalloendopeptidases / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D016133:Polymerase Chain Reaction; D012513:Sarcoma, Experimental / Q000201:enzymology / Q000473:pathology / Q000556:secondary*; D013482:Superoxide Dismutase / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D013481:Superoxides / Q000494:pharmacology; D014162:Transfection / Q000235:genetics; D014407:Tumor Cells, Cultured / Q000378:metabolism
D016373:DNA, Antisense; D004273:DNA, Neoplasm; D013481:Superoxides; D013482:Superoxide Dismutase; D017364:Collagenases; D018093:Gelatinases; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9