Abstract 710: The efficacy of tumor-targeting Salmonella typhimurium A1-R on bone metastasis

Abstract

Abstract We have previously developed a genetically-modified bacterial strain of Salmonella typhimurium (A1-R), which expresses GFP. In this study, we measured the efficacy of A1-R on breast cancer bone metastasis. We established an early-stage bone-metastasis model in nude mice by cardiac injection and a late-stage model by injection into the intramedullary cavity of the tibia using MDA-MB-435 human breast cancer cells (Human breast cancer cell lines co-express neuronal, epithelial, and melanocytic differentiation markers in vitro and in vivo. PLoS One 5, e9712, 2010). Both mouse models of bone metastasis were treated with A1-R. Fluorescence imaging of the mice was performed to visualize the metastatic bone lesions. In a first set of experiments, we showed that A1-R invaded and replicated intracellularly in MDA-MB-435-GFP cells in vitro. A1-R dose-dependently inhibited proliferation of MDA-MB-435-GFP cells. In the early-stage bone-metastasis model, A1-R significantly improved metastasis-free survival. In the advanced-stage bone-metastasis model, A1-R significantly inhibited the growth of the metastatic lesions. These data indicated that A1-R is useful to prevent and inhibit the growth of metastatic breast cancer bone tumors. Citation Format: Shinji Miwa, Ming Zhao, Shuya Yano, Yong Zhang, Fuminari Uehara, Yasunori Matsumoto, Yukihiko Hiroshima, Mako Yamamoto, Hiroaki Kimura, Katsuhiro Hayashi, Hiroyuki Tsuchiya, Robert M. Hoffman. The efficacy of tumor-targeting Salmonella typhimurium A1-R on bone metastasis. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 710. doi:10.1158/1538-7445.AM2014-710