Direct targeting of tumor cell F1F0 ATP-synthase by radioiodine angiostatin in vitro and in vivo

被引:19
|
作者
Jung, Kyung-Ho
Song, Sung-Hee
Paik, Jin-Young
Koh, Bong-Ho
Choe, Yearn Seong
Lee, Eun Jung
Kim, Byung-Tae
Lee, Kyung-Han
机构
[1] Samsung Med Ctr, Dept Nucl Med, Seoul 135710, South Korea
[2] Sungkyunkwan Univ, Samsung Med Ctr, Dept Nucl Med, Seoul, South Korea
关键词
tumor; angiostatin; ATP synthase; angiogenesis; radioiodine;
D O I
10.1089/cbr.2007.369
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Recent discoveries have identified endothelial cell-surface F1F0 adenosine triphosphate (ATP) synthase as the key target for angiostatin (AST) action. As this enzyme is also present on tumor cells, we investigated whether radiolabeled AST may directly target cancer cell-surface ATP synthase in vitro and in vivo. Methods: Cell-binding characteristics of I-125-AST was evaluated on human umbilical vein endothelial (HUVE) and SNU-C5 colon carcinoma cells. The molecular target for binding was investigated with anti ATP synthase antibodies and RGDyV. Biodistribution and imaging experiments were performed in mice xenografted with carcinoma and sarcoma tumors. Tumor localization of ATP synthase and exogenous AST was compared via double immunostaining. Results: Both HUVE and SNU-C5 cells showed specific I-125-AST binding that was dose-dependently inhibited by excess AST, with IC50 values of 3.5 and 0.2 mu M, respectively. Both cell types stained positive for ATP synthase and demonstrated an approximately 50% reduction in AST binding by antibodies against the alpha- and beta-subunit of the enzyme: I-123-AST injected in mice allowed for the clear tumor visualization with significant tumor accumulation and uptake ratios. Immunostaining revealed a localization of exogenous AST to closely correlate to that of tumor-cell ATP synthase. Conclusions: AST can directly target tumor-cell ATP synthase, and AST imaging may thus be useful for monitoring tumor ATP synthase expression.
引用
收藏
页码:704 / 712
页数:9
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