Tumor invasion of Salmonella enterica serovar Typhimurium is accompanied by strong hemorrhage promoted by TNF-alpha.
BACKGROUND
Several facultative anaerobic bacteria with potential therapeutic abilities are known to preferentially colonize solid tumors after systemic administration. How they efficiently find and invade the tumors is still unclear. However, this is an important issue to be clarified when bacteria should be tailored for application in cancer therapy.


RESULTS
We describe the initial events of colonization of an ectopic transplantable tumor by Salmonella enterica serovar Typhimurium. Initially, after intravenous administration, bacteria were found in blood, spleen, and liver. Low numbers were also detected in tumors associated with blood vessels as could be observed by immunohistochemistry. A rapid increase of TNF-alpha in blood was observed at that time, in addition to other pro-inflammatory cytokines. This induced a tremendous influx of blood into the tumors by vascular disruption that could be visualized in H&E stainings and quantified by hemoglobin measurements of tumor homogenate. Most likely, together with the blood, bacteria were flushed into the tumor. In addition, blood influx was followed by necrosis formation, bacterial growth, and infiltration of neutrophilic granulocytes. Depletion of TNF-alpha retarded blood influx and delayed bacterial tumor-colonization.


CONCLUSIONS
Our findings emphasize similarities between Gram-negative tumor-colonizing bacteria and tumor vascular disrupting agents and show the involvement of TNF-alpha in the initial phase of tumor-colonization by bacteria.
Leschner
Sara
S
Molecular Immunology, HZI-Helmholtz Centre for Infection Research, Braunschweig, Germany. sara.leschner@helmholtz-hzi.de
Westphal
Kathrin
K
Dietrich
Nicole
N
Viegas
Nuno
N
Jablonska
Jadwiga
J
Lyszkiewicz
Marcin
M
Lienenklaus
Stefan
S
Falk
Werner
W
Gekara
Nelson
N
Loessner
Holger
H
Weiss
Siegfried
S
D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced / Q000382:microbiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental / Q000382:microbiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019779:Salmonella enterica / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D017931:DNA Primers; D014409:Tumor Necrosis Factor-alpha
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