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

被引:20
作者
Tanaka, M [1 ]
Kogawa, K [1 ]
Nakamura, K [1 ]
Nishihori, Y [1 ]
Kuribayashi, K [1 ]
Hagiwara, S [1 ]
Muramatsu, H [1 ]
Sakamaki, S [1 ]
Niitsu, Y [1 ]
机构
[1] Sapporo Med Univ, Sch Med, Dept Internal Med 4, Chuo Ku, Sapporo, Hokkaido 0600061, Japan
关键词
gene therapy; metastasis; extracellular superoxide dismutase; autologous fibroblasts; retrovirus;
D O I
10.1038/sj.gt.3301362
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 longlasting, 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.
引用
收藏
页码:149 / 156
页数:8
相关论文
共 30 条
[1]  
ADACHI T, 1989, J BIOL CHEM, V264, P8537
[2]   Sinusoidal endothelium release of hydrogen peroxide enhances very late antigen-4-mediated melanoma cell adherence and tumor cytotoxicity during interleukin-1 promotion of hepatic melanoma metastasis in mice [J].
Anasagasti, MJ ;
Alvarez, A ;
Martin, JJ ;
Mendoza, L ;
VidalVanaclocha, F .
HEPATOLOGY, 1997, 25 (04) :840-846
[3]   Production of superoxide by human malignant melanoma cells [J].
Bittinger, F ;
Gonzalez-Garcia, JL ;
Klein, CL ;
Brochhausen, C ;
Offner, F ;
Kirkpatrick, CJ .
MELANOMA RESEARCH, 1998, 8 (05) :381-387
[4]  
FIDLER IJ, 1990, CANCER RES, V50, P6130
[5]   Experimental study on the role of osteoclasts and free radicals in the mandibular invasion of VX2 carcinoma in Japanese white rabbits [J].
Fujimiya, K ;
Sugihara, K ;
Nishikawa, T .
BONE, 1997, 20 (03) :245-250
[6]   Vascular expression of extracellular superoxide dismutase in atherosclerosis [J].
Fukai, T ;
Galis, ZS ;
Meng, XP ;
Parthasarathy, S ;
Harrison, DG .
JOURNAL OF CLINICAL INVESTIGATION, 1998, 101 (10) :2101-2111
[7]   SYNTHESIS OF A SUPEROXIDE-DISMUTASE DERIVATIVE THAT CIRCULATES BOUND TO ALBUMIN AND ACCUMULATES IN TISSUES WHOSE PH IS DECREASED [J].
INOUE, M ;
EBASHI, I ;
WATANABE, N ;
MORINO, Y .
BIOCHEMISTRY, 1989, 28 (16) :6619-6624
[8]   PLASMA-CLEARANCE OF HUMAN EXTRACELLULAR-SUPEROXIDE DISMUTASE-C IN RABBITS [J].
KARLSSON, K ;
MARKLUND, SL .
JOURNAL OF CLINICAL INVESTIGATION, 1988, 82 (03) :762-766
[9]  
KARLSSON K, 1998, BIOCHEM J, V255, P233
[10]   Enhanced inhibition of experimental metastasis by the combination chemotherapy of Cu-ZnSOD and adriamycin [J].
Kogawa, K ;
Muramatsu, H ;
Tanaka, M ;
Nishihori, Y ;
Hagiwara, S ;
Kuribayashi, K ;
Nakamura, K ;
Koike, K ;
Sakamaki, S ;
Niitsu, Y .
CLINICAL & EXPERIMENTAL METASTASIS, 1999, 17 (03) :239-244