Vasculature Disruption Enhances Bacterial Targeting of Autochthonous Tumors
| Autor: | Daniel A. Saltzman, Jeremy Drees, Lance B. Augustin, Janet L. Schottel, Michael J. Mertensotto |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Pathology
medicine.medical_specialty Necrosis autochthonous Transgene tumor-targeting 4T1 BALB-neuT necrosis breast cancer Breast cancer Salmonella medicine combretastatin A-4 Vector (molecular biology) spontaneous Short Research Communication biology business.industry Cancer medicine.disease biology.organism_classification Transplantation Oncology Salmonella enterica Cancer research cancer therapy medicine.symptom business Bacteria vasculature disruption |
| Zdroj: | Journal of Cancer |
| ISSN: | 1837-9664 |
| Popis: | Attenuated Salmonella enterica serovar Typhimurium (S. Typhimurium) has been developed as a vector to deliver therapeutic agents to tumors. The potential of S. Typhimurium in cancer therapy is largely due to its reported propensity to accumulate at greater than 1,000-fold higher concentrations in tumors relative to healthy tissues. In this study, we compared bacterial colonization of tumors in a subcutaneous transplantation model with a more clinically relevant autochthonous tumor model. Following intravenous administration of attenuated S. Typhimurium strain SL3261, we observed approximately 10,000-fold less bacteria in autochthonous tumors that sporadically develop in transgenic BALB-neuT mice compared to tumors developed from subcutaneous transplantation of 4T1 murine breast cancer cells in BALB/c mice. Treatment of BALB-neuT mice with a vasculature-disrupting agent (VDA) prior to bacterial treatment caused necrosis of tumor tissue and significantly increased the bacterial targeting of autochthonous tumors by approximately 1,000-fold. These observations emphasize the importance of appropriate model selection in developing bacteria-based cancer therapies and demonstrate the potential of combining VDA pre-treatment with bacteria to facilitate targeting of clinically relevant tumors. |
| Databáze: | OpenAIRE |
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