Effect of Salmonella enterica serovar Typhimurium VNP20009 and VNP20009 with restored chemotaxis on 4T1 mouse mammary carcinoma progression
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Sheryl L. Coutermarsh-Ott1,*, Katherine M. Broadway2,*, Birgit E. Scharf2, Irving C. Allen1
1Virginia Tech, VA-MD College of Veterinary Medicine, Department of Biomedical Sciences and Pathobiology, Blacksburg, VA, USA
2Virginia Tech, Department of Biological Sciences, Blacksburg, VA, USA
*These authors contributed equally to this work
Irving C. Allen, email: [email protected]
Birgit E. Scharf, email: [email protected]
Keywords: bacterial therapeutic, breast cancer, chemotaxis, CheY, metastasis
Received: October 12, 2016 Accepted: March 27, 2017 Published: April 04, 2017
A variety of bacterial strains have been evaluated as bio-therapeutic and immunomodulatory agents to treat cancer. One such strain, Salmonella enterica serovar Typhimurium VNP20009, which is attenuated by a purine auxotrophic mutation and modified lipid A, is characterized in previous models as a safely administered, tumor colonizing agent. However, earlier work tended to use less aggressive cancer cell lines and immunocompromised animal models. Here, we investigated the safety and efficacy of VNP20009 in a highly malignant murine model of human breast cancer. Additionally, as VNP20009 has recently been found to have a defective chemotaxis system, we tested whether restoring chemotaxis would improve anti-cancer properties in this model system. Exposure to VNP20009 had no significant effect on primary mammary tumor size or pulmonary metastasis, and the tumor colonizing process appeared chemotaxis independent. Moreover, tumor-bearing mice exposed to Salmonella exhibited increased morbidity that was associated with significant liver disease. Our results suggest that VNP20009 may not be safe or efficacious when used in aggressive, metastatic breast cancer models utilizing immunocompetent animals.
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