Vessel destruction by tumor-targeting Salmonella typhimurium A1-R is enhanced by high tumor vascularity
Vessel destruction by tumor-targeting Salmonella typhimurium A1-R is enhanced by high tumor vascularity
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DOI：
10.4161/cc.9.22.13744
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发表时间：
2010-11-15
期刊：
影响因子：
4.3
通讯作者：
Zhao, Ming
中科院分区：
文献类型：
--
作者：
Liu, Fang;Zhang, Lei;Zhao, Ming
我们实验室此前已开发出一种针对肿瘤的鼠伤寒沙门氏菌双营养缺陷型突变体，称为A1-R。本报告表明，鼠伤寒沙门氏菌 A1-R 会破坏肿瘤血管，并且这种作用在具有高血管分布的肿瘤中得到增强。将表达红色荧光蛋白（RFP）的Lewis肺癌细胞（LLC-RFP）皮下移植到巢蛋白驱动的绿色荧光蛋白（ND-GFP）转基因裸鼠的耳部、背部皮肤和足垫中，在新生血管中选择性表达GFP。颜色编码的体内成像表明 LLC-RFP 耳肿瘤的细胞密度最高，而足垫肿瘤的细胞密度最低。耳部肿瘤的血管比背部或足垫的肿瘤更丰富。通过尾静脉注射 A1-R 细菌治疗荷瘤小鼠。耳朵中的肿瘤是对细菌治疗最早做出反应的，并且在 A1-R 给药后的第二天出现严重出血。背部生长的肿瘤是对细菌治疗反应第二快的肿瘤，在 A1-R 给药 3 天后出现坏死。足垫中生长的肿瘤具有最少的血管分布，并且是对 A1-R 的最后反应者。因此，肿瘤血管分布与A1-R的肿瘤功效呈正相关。目前的研究表明，细菌对肿瘤的功效涉及血管破坏，这取决于肿瘤血管分布的程度。
Our laboratory has previously developed a tumor-targeting double-auxotrophic mutant of Salmonella typhimurium termed A1-R. The present report demonstrates that S. typhimurium A1-R destroys tumor blood vessels and this is enhanced in tumors with high vascularity. Red fluorescent protein (RFP)-expressing Lewis lung cancer cells (LLC-RFP) were transplanted subcutaneously in the ear, back skin and footpad of nestin-driven green fluorescent protein (ND-GFP) transgenic nude mice, which selectively express GFP in nascent blood vessels. Color-coded in vivo imaging demonstrated that the LLC-RFP ear tumor had the highest cell density and the footpad tumor had the least. The ear tumor had more abundant blood vessels than that on the back or footpad. The tumor-bearing mice were treated with A1-R bacteria via tail-vein injection. Tumors in the ear were the earliest responders to bacterial therapy and hemorrhaged severely the day after A1-R administration. Tumors growing in the back were the second fastest responders to bacterial treatment and appeared necrotic 3 days after A1-R administration. Tumors growing in the footpad had the least vascularity and were the last responders to A1-R. Therefore, tumor vascularity correlated positively with tumor efficacy of A1-R. The present study suggests that bacteria efficacy on tumors involves vessel destruction which depends on the extent of vascularity of the tumor.