Tumor-targeting Salmonella typhimurium A1-R arrests growth of breast-cancer brain metastasis

Oncotarget. 2015 Feb 20;6(5):2615-22. doi: 10.18632/oncotarget.2811.

Abstract

Brain metastasis is a morbid, treatment-resistant, end-stage frequent occurrence in breast cancer patients. The aim of this study was to evaluate the efficacy of tumor-targeting Salmonella typhimurium A1-R on breast cancer brain metastases. High brain-metastatic variants of murine 4T1 breast cancer cells expressing red fluorescent protein (RFP) were injected orthotopically in the mammary fat pad in non-transgenic nude mice or in the left ventricle of non-transgenic nude mice and transgenic nude mice expressing nestin-driven green fluorescent protein (ND-GFP). ND-GFP mice express GFP in nascent blood vessels. In the orthotopically-injected mice, the primary tumor was surgically-resected in order to allow brain metastasis to develop. At various time points, the tumors and vasculature in the brain were imaged by confocal and stereo fluorescence microscopy. Some of the breast cancer cells that reached the brain extravasated and grew perivascularly and some of the cells proliferated within the vasculature. S. typhimurium A1-R significantly inhibited brain metastasis in both metastatic models and increased survival of the orthotopically-transplanted, primary-tumor-resected mice (p<0.05). The results of the present study suggest the clinical potential of bacterial therapy of breast cancer brain metastasis.

Publication types

  • Evaluation Study

MeSH terms

  • Animals
  • Brain Neoplasms / microbiology*
  • Brain Neoplasms / prevention & control*
  • Brain Neoplasms / secondary
  • Breast Neoplasms / pathology
  • Breast Neoplasms / therapy*
  • Cell Cycle Checkpoints*
  • Cell Line, Tumor
  • Female
  • Green Fluorescent Proteins / biosynthesis*
  • Green Fluorescent Proteins / genetics
  • Luminescent Proteins / biosynthesis
  • Luminescent Proteins / genetics
  • Mice, Inbred C57BL
  • Mice, Nude
  • Mice, Transgenic
  • Nestin / genetics
  • Salmonella typhimurium / genetics
  • Salmonella typhimurium / metabolism
  • Salmonella typhimurium / pathogenicity*
  • Time Factors
  • Transfection

Substances

  • Luminescent Proteins
  • Nestin
  • red fluorescent protein
  • Green Fluorescent Proteins