Targeting Orthotopic Glioma in Mice with Genetically Engineered Salmonella typhimurium.
OBJECTIVE
With the growing interests of bacteria as a targeting vector for cancer treatment, diverse genetically engineered Salmonella has been reported to be capable of targeting primary or metastatic tumor regions after intravenous injection into mouse tumor models. The purpose of this study was to investigate the capability of the genetically engineered Salmonella typhimurium (S. typhimurium) to access the glioma xenograft, which was monitored in mouse brain tumor models using optical bioluminescence imaging technique.


METHODS
U87 malignant glioma cells (U87-MG) stably transfected with firefly luciferase (Fluc) were implanted into BALB/cAnN nude mice by stereotactic injection into the striatum. After tumor formation, attenuated S. typhimurium expressing bacterial luciferase (Lux) was injected into the tail vein. Bioluminescence signals from transfected cells or bacteria were monitored using a cooled charge-coupled device camera to identify the tumor location or to trace the bacterial migration. Immunofluorescence staining was also performed in frozen sections of mouse glioma xenograft.


RESULTS
The injected S. typhimurium exclusively localized in the glioma xenograft region of U87-MG-bearing mouse. Immunofluorescence staining also demonstrated the accumulation of S. typhimurium in the brain tumors.


CONCLUSIONS
The present study demonstrated that S. typhimurium can target glioma xenograft, and may provide a potentially therapeutic probe for glioma.
Brain Tumor Research Laboratory and Department of Neurosurgery, Chonnam National University Research Institute, Chonnam National University Hwasun Hospital and Medical School, Hwasun, Korea.
Min
M
Wen
Brain Tumor Research Laboratory and Department of Neurosurgery, Chonnam National University Research Institute, Chonnam National University Hwasun Hospital and Medical School, Hwasun, Korea.
Shin
S
Jung
Brain Tumor Research Laboratory and Department of Neurosurgery, Chonnam National University Research Institute, Chonnam National University Hwasun Hospital and Medical School, Hwasun, Korea.
Kyung-Sub
KS
Moon
Laboratory of In Vivo Molecular Imaging (LOVMI) and Department of Nuclear Medicine, Chonnam National University Research Institute, Chonnam National University Hwasun Hospital and Medical School, Hwasun, Korea.
Shen Nan
SN
Jiang
Brain Tumor Research Laboratory and Department of Neurosurgery, Chonnam National University Research Institute, Chonnam National University Hwasun Hospital and Medical School, Hwasun, Korea.
Song-Yuan
SY
Li
Laboratory of In Vivo Molecular Imaging (LOVMI) and Department of Nuclear Medicine, Chonnam National University Research Institute, Chonnam National University Hwasun Hospital and Medical School, Hwasun, Korea.
Jung-Joon
JJ
Min
Cancer targeting; Mouse glioma model; Optical bioluminescence imaging; Salmonella typhimurium; U87-MG