Abstract

Abstract We previously demonstrated a color-coded angiogenesis imaging model using Gelfoam® implanted in nestin-driven green fluorescent protein (ND-GFP) nude mice in which nascent blood vessels express GFP. In this assay, we demonstrated osteosarcoma promotes angiogenesis. We report here that Salmonella typhimurium A1-R (S. typhimurium A1-R) inhibits angiogenesis of osteosarcoma cells in the Gelfoam® angiogenesis assay in ND-GFP mice. Gelfoam® was transplanted subcutaneously in the flank of transgenic ND-GFP nude mice. Seven days after transplantation, skin flaps were made and 143B human osteosarcoma cells, expressing red fluorescent protein (RFP), were injected in the transplanted Gelfoam®. After establishment of tumor in the Gelfoam®, the control group mice were treated with PBS by tail vein injection. The treated group was treated by S. typhimurium A1-R, also by tail vein injection. Skin flaps were made at days 14, 21, and 28 after transplantation of the Gelfoam® in order to allow imaging of vascularization. The OV100 variable magnification small animal imaging system and FV1000 confocal fluorescence microscope were used to visualize vascularization. Nascent blood vessels grew in the Gelfoam® in a time-dependent manner. A random 3 fields were quantified in each group. The mean length of ND-GFP-expressing blood vessels in the Gelfoam® in mice were treated with S. typhimurium A1-R was 9.40, 12.40, and 10.12 mm/mm2, at days 14, 21, and 28, respectively. The mean total length of ND-GFP-expressing blood vessels in the Gelfoam® in mice of the control group were 8.86, 14.50, and 15.81 mm/mm2 on day 14, 21, and 28, respectively. ND-GFP expressing blood vessels of the mice in the osteosarcoma cells treated with S. typhimurium A1-R had shorter vessels than the control group (on day-28, P<0.05). There was not a significant difference in tumor size between the 2 groups, thereby indicating a specific inhibition of angiogenesis by S. typhimurium A1-R. In the present study, we reported that S. typhimurium A1-R inhibited angiogenesis of human osteosarcoma cells in the in vivo Gelfoam® color-coded imaging assay. Citation Format: Tasuku Kiyuna, Yasunori Tome, Takashi Murakami, Ming Zhao, Fuminori Kanaya, Robert M. Hoffman. Inhibition of tumor angiogenesis by Salmonella typhimurium A1-R in the in vivo Gelfoam color-coded imaging assay [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2874. doi:10.1158/1538-7445.AM2017-2874

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