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.
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.
Tanaka
M
M
Fourth Department of Internal Medicine, Sapporo Medical University School of Medicine, South-1, West-16, Chuo-ku, Sapporo, Hokkaido, 060-0061, Japan.
Kogawa
K
K
Nakamura
K
K
Nishihori
Y
Y
Kuribayashi
K
K
Hagiwara
S
S
Muramatsu
H
H
Sakamaki
S
S
Niitsu
Y
Y
D000818:Animals; D018827:Carcinoma, Lewis Lung / Q000473:pathology / Q000556:secondary / Q000628:therapy; D018929:Cell Culture Techniques; D002455:Cell Division; D003470:Culture Media; D018076:DNA, Complementary / Q000235:genetics; D005240:Feasibility Studies; D005347:Fibroblasts / Q000637:transplantation; D015870:Gene Expression; D015316:Genetic Therapy / Q000379:methods*; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008175:Lung Neoplasms / Q000473:pathology / Q000556:secondary* / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D009368:Neoplasm Transplantation; D012333:RNA, Messenger / Q000235:genetics; D012513:Sarcoma, Experimental / Q000473:pathology / Q000556:secondary / Q000628:therapy; D013482:Superoxide Dismutase / Q000235:genetics* / Q000378:metabolism; D014161:Transduction, Genetic
D003470:Culture Media; D018076:DNA, Complementary; D007527:Isoenzymes; D012333:RNA, Messenger; D013482:Superoxide Dismutase