Anti-metastatic gene therapy utilizing subcutaneous inoculation of EC-SOD gene transduced autologous fibroblast suppressed lung metastasis of Meth-A cells and 3LL cells in mice.

Tanaka, M; Kogawa, K; Nakamura, K; Nishihori, Y; Kuribayashi, K; Hagiwara, S; Muramatsu, H; Sakamaki, S; Niitsu, Y

We have previously reported that superoxide stimulates the motility of tumor cells and the administration of Cu-Zn superoxide dismutase (SOD) significantly suppresses metastasis. However, ideally, anti-metastatic therapy should be long-lasting, systemically effective and have low toxicity. The half-life of Cu-Zn SOD in plasma is so short that it cannot provide long-lasting effects. Therefore, in this study we have developed a gene therapy in a mouse model utilizing extracellular SOD (EC-SOD), which is the most prevalent SOD isoenzyme in extracellular fluids. We retrovirally transfected fibroblasts (syngeneic) with the EC-SOD gene and established EC-SOD-secreting fibroblasts. Inoculation of EC-SOD-secreting fibroblasts suppressed both artificial and spontaneous metastatic lung nodules in mouse metastasis models. These data indicate the feasibility of anti-metastatic gene therapy utilizing the EC-SOD gene. Gene Therapy (2001) 8, 149–156.

METASTASIS; EXTRACELLULAR fluid; SUPEROXIDE dismutase; FIBROBLASTS; GENE therapy; THERAPEUTICS

Gene Therapy, 2001, Vol 8, Issue 2, p149

0969-7128

Academic Journal

10.1038/sj.gt.3301362