Tumor-targeting Salmonella typhimurium A1-R Inhibits Osteosarcoma Angiogenesis in the In Vivo Gelfoam® Assay Visualized by Color-coded Imaging
Tumor-targeting Salmonella typhimurium A1-R Inhibits Osteosarcoma Angiogenesis in the In Vivo Gelfoam® Assay Visualized by Color-coded Imaging
复制标题
DOI：
10.21873/anticanres.12203
复制
发表时间：
2018-01-01
影响因子：
2
通讯作者：
Hoffman, Robert M.
中科院分区：
文献类型：
--
作者：
Kiyuna, Tasuku;Tome, Yasunori;Hoffman, Robert M.
背景：我们之前开发了一种彩色编码成像模型，该模型可以量化新生血管的长度，该模型使用Gelfoam (R)植入巢驱动绿色荧光蛋白（ND-GFP）裸鼠。在这个模型中，新生血管选择性地表达GFP。我们之前也在这个实验中表明骨肉瘤细胞促进血管生成。我们之前也证明了肿瘤靶向细菌鼠伤寒沙门菌A1-R （S. typhimurium A1-R）可以在小鼠模型中抑制或逆转所有测试的肿瘤类型。本研究的目的是在体内明胶泡沫(R)彩色编码成像实验中确定鼠伤寒沙门氏菌A1-R是否能抑制骨肉瘤血管生成。材料与方法：将明胶泡沫塑料(R)植入ND-GFP裸鼠皮下。植入7天后制作皮瓣，将表达红色荧光蛋白（RFP）的143B-RFP人骨肉瘤细胞注射到植入的明胶泡沫中。在明胶泡沫(R)中建立肿瘤后，对照组小鼠通过尾静脉注射磷酸盐缓冲盐水（iv），实验组小鼠通过鼠型沙门菌A1-R iv治疗，在植入明胶泡沫(R)后的第7、14、21和28天制作皮瓣，使用可变放大的小动物成像系统和共聚焦荧光显微镜对明胶泡沫(R)中的血管形成进行成像。结果：随着时间的推移，两组新生血管表达ND-GFP延伸至明胶泡沫(R)。然而，在第28天，鼠伤寒沙门氏菌A1-R处理明显抑制了新生血管的生长程度。结论：鼠伤寒沙门氏菌A1-R具有抗血管生成靶向治疗骨肉瘤的潜力。
Background: We previously developed a color-coded imaging model that can quantify the length of nascent blood vessels using Gelfoam (R) implanted in nestin-driven green fluorescent protein (ND-GFP) nude mice. In this model, nascent blood vessels selectively express GFP. We also previously showed that osteosarcoma cells promote angiogenesis in this assay. We have also previously demonstrated the tumor-targeting bacteria Salmonella typhimurium A1-R (S. typhimurium A1-R) can inhibit or regress all tested tumor types in mouse models. The aim of the present study was to determine if S. typhimurium A1-R could inhibit osteosarcoma angiogenesis in the in vivo Gelfoam (R) color-coded imaging assay. Materials and Methods: Gelfoam (R) was implanted subcutaneously in ND-GFP nude mice. Skin flaps were made 7 days after implantation and 143B-RFP human osteosarcoma cells expressing red fluorescent protein (RFP) were injected into the implanted Gelfoam. After establishment of tumors in the Gelfoam (R), control-group mice were treated with phosphate buffered saline via tail-vein injection (iv) and the experimental group was treated with S. typhimurium A1-R iv Skin flaps were made at day 7, 14, 21, and 28 after implantation of the Gelfoam (R) to allow imaging of vascularization in the Gelfoam (R) using a variable-magnification small-animal imaging system and confocal fluorescence microscopy. Results: Nascent blood vessels expressing ND-GFP extended into the Gelfoam (R) over time in both groups. However, the extent of nascent blood-vessel growth was significantly inhibited by S. typhimurium A1-R treatment by day 28. Conclusion: The present results indicate S. typhimurium A1-R has potential for anti-angiogenic targeted therapy of osteosarcoma.