Inhibition of spontaneous and experimental lung metastasis of soft-tissue sarcoma by tumor-targeting Salmonella typhimurium A1-R

Shinji Miwa, Yong Zhang, Kyung Eun Baek, Fuminari Uehara, Shuya Yano, Mako Yamamoto, Yukihiko Hiroshima, Yasunori Matsumoto, Hiroaki Kimura, Katsuhiro Hayashi, Norio Yamamoto, Michael Bouvet, Hiroyuki Tsuchiya, Robert M. Hoffman, Ming Zhao

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35 Citations (Scopus)

Abstract

Prognosis of patients with lung metastases of soft-tissue sarcoma is still poor. Therefore, novel systemic therapy is needed to improve the survival of soft-tissue sarcoma. In the present study, tumor-targeting therapy with a genetically-modified auxotrophic strain of Salmonella typhimurium, termed A1-R, was evaluated. Mouse models of primary soft tissue sarcoma and spontaneous lung metastasis were obtained by orthotopic intra-muscular injection of HT1080-RFP human fibrosarcoma cells. S. typhimurium A1-R was administered from day 14, once a week for two weeks. On day 28, lung samples were excised and observed with a fluorescence imaging system. The number of lung metastasis was 8.8 ± 3.4 in the untreated group and 0.8 ± 0.8 in the treated group (P = 0.024). A mouse model of experimental lung metastasis was obtained by tail vein injection of HT1080-RFP cells. The mice were treated with S. typhimurium A1-R (i.v.) on day 7, once a week for three weeks. S. typhimurium A1-R significantly reduced lung metastases and improved overall survival (P = 0.004). S. typhimurium A1-R bacterial therapy has future potential for treating advanced soft tissue sarcoma and improving prognosis of patients with lung metastasis.

Original languageEnglish
Pages (from-to)12849-12861
Number of pages13
JournalOncotarget
Volume5
Issue number24
DOIs
Publication statusPublished - 2014
Externally publishedYes

Keywords

  • Bacterial therapy
  • HT-1080
  • Lung metastasis
  • Nude mice
  • Orthotopic model

ASJC Scopus subject areas

  • Oncology

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  • Cite this

    Miwa, S., Zhang, Y., Baek, K. E., Uehara, F., Yano, S., Yamamoto, M., Hiroshima, Y., Matsumoto, Y., Kimura, H., Hayashi, K., Yamamoto, N., Bouvet, M., Tsuchiya, H., Hoffman, R. M., & Zhao, M. (2014). Inhibition of spontaneous and experimental lung metastasis of soft-tissue sarcoma by tumor-targeting Salmonella typhimurium A1-R. Oncotarget, 5(24), 12849-12861. https://doi.org/10.18632/oncotarget.2561