Vessel destruction by tumor-targeting Salmonella typhimurium A1-R is enhanced by high tumor vascularity

Cell Cycle. 2010 Nov 15;9(22):4518-24. doi: 10.4161/cc.9.22.13744.

Abstract

Our laboratory has previously developed a tumor-targeting double-auxotrophic mutant of Salmonella typhimurium termed A1-R. The present report demonstrates that S. typhimurium A1-R destroys tumor blood vessels and this is enhanced in tumors with high vascularity. Red fluorescent protein (RFP)-expressing Lewis lung cancer cells (LLC-RFP) were transplanted subcutaneously in the ear, back skin, and footpad of nestin-driven green fluorescent protein (ND-GFP) transgenic nude mice, which selectively express GFP in nascent blood vessels. Color-coded in vivo imaging demonstrated that the LLC-RFP ear tumor had the highest cell density and the footpad tumor had the least with the ear tumor having more abundant blood vessels than that on the back or footpad. The tumor-bearing mice were treated with A1-R bacteria via tail-vein injection. Tumors in the ear were the earliest responders to bacterial therapy and hemorrhaged severely the day after A1-R administration. Tumors growing in the back were the second fastest responders to bacterial treatment and appeared necrotic 3 days after A1-R administration. Tumors growing in the footpad had the least vascularity and were the last responders to A1-R. Therefore, tumor vascularity correlated positively with tumor efficacy of A1-R. The present study suggests that bacteria efficacy on tumors involved vessel destruction which depends on the extent of vascularity of the tumor.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Vessels / microbiology
  • Blood Vessels / pathology
  • Carcinoma, Lewis Lung / blood supply*
  • Carcinoma, Lewis Lung / pathology
  • Carcinoma, Lewis Lung / therapy
  • Cell Line, Tumor
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Intermediate Filament Proteins / genetics
  • Intermediate Filament Proteins / metabolism
  • Luminescent Proteins / genetics
  • Luminescent Proteins / metabolism
  • Lung Neoplasms / blood supply*
  • Lung Neoplasms / pathology
  • Lung Neoplasms / therapy
  • Mice
  • Mice, Nude
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Nestin
  • Platelet Endothelial Cell Adhesion Molecule-1 / metabolism
  • Salmonella typhimurium / genetics*
  • Salmonella typhimurium / growth & development
  • Salmonella typhimurium / pathogenicity
  • Transplantation, Heterologous

Substances

  • Intermediate Filament Proteins
  • Luminescent Proteins
  • Nerve Tissue Proteins
  • Nes protein, mouse
  • Nestin
  • Platelet Endothelial Cell Adhesion Molecule-1
  • red fluorescent protein
  • Green Fluorescent Proteins