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

Oncotarget. 2014 Dec 30;5(24):12849-61. doi: 10.18632/oncotarget.2561.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Disease Models, Animal
  • Female
  • Fibrosarcoma / microbiology
  • Fibrosarcoma / pathology
  • Fibrosarcoma / therapy
  • Humans
  • Lung Neoplasms / microbiology
  • Lung Neoplasms / pathology
  • Lung Neoplasms / secondary*
  • Lung Neoplasms / therapy*
  • Mice
  • Mice, Nude
  • Neoplasm Metastasis
  • Prognosis
  • Salmonella typhimurium / physiology*
  • Sarcoma / microbiology
  • Sarcoma / pathology
  • Sarcoma / therapy*
  • Xenograft Model Antitumor Assays