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Effect of Salmonella treatment on an implanted tumor (CT26) in a mouse model
Misun Yun1, SangO Pan, Sheng-Nan Jiang
1Departments of Microbiology, Chonnam National University Medical School, Gwangju, 501-746, Republic of Korea.
Abstract:
The use of bacteria has contributed to recent advances in targeted cancer therapy especially for its tumor-specific accumulation and proliferation. In this study, we investigated the molecular events following bacterial therapy using an attenuated Salmonella Typhimurium defective in ppGpp synthesis (ΔppGpp), by analyzing those proteins differentially expressed in tumor tissues from treated and untreated mice. CT26 murine colon cancer cells were implanted in BALB/c mice and allowed to form tumors. The tumor-bearing mice were treated with the attenuated Salmonella Typhimurium. Tumor tissues were analyzed by 2D-PAGE. Fourteen differentially expressed proteins were identified by mass spectrometry. The analysis revealed that cytoskeletal components, including vimentin, drebrin-like protein, and tropomyosin-alpha 3, were decreased while serum proteins related to heme or iron metabolism, including transferrin, hemopexin, and haptoglobin were increased. Subsequent studies revealed that the decrease in cytoskeletal components occurred at the transcriptional level and that the increase in heme and iron metabolism proteins occurred in liver. Most interestingly, the same pattern of increased expression of transferrin, hemopexin, and haptoglobin was observed following radiotherapy at the dosage of 14 Gy.
Insights
Bacterial cancer therapy with attenuated Salmonella Typhimurium alters protein expression in tumors, decreasing cytoskeletal proteins and increasing iron metabolism proteins. This response pattern was also observed following radiotherapy.
Area of Science:
- Oncology
- Microbiology
- Proteomics
Background:
- Bacteria-based cancer therapy leverages tumor-specific accumulation and proliferation.
- Attenuated Salmonella Typhimurium is a promising agent for targeted cancer treatment.
Purpose of the Study:
- To investigate the molecular changes in tumor tissues after treatment with attenuated Salmonella Typhimurium (ΔppGpp).
- To identify differentially expressed proteins in tumors following bacterial therapy.
Main Methods:
- CT26 murine colon cancer cells were implanted in BALB/c mice.
- Tumor-bearing mice were treated with attenuated Salmonella Typhimurium.
- Differential protein expression in tumor tissues was analyzed using 2D-PAGE and mass spectrometry.
Main Results:
- Fourteen differentially expressed proteins were identified.
- Decreased expression of cytoskeletal proteins (vimentin, drebrin-like protein, tropomyosin-alpha 3) at the transcriptional level.
- Increased expression of serum proteins involved in heme/iron metabolism (transferrin, hemopexin, haptoglobin) in the liver.
- Similar upregulation of transferrin, hemopexin, and haptoglobin was observed after 14 Gy radiotherapy.
Conclusions:
- Bacterial therapy with attenuated Salmonella Typhimurium induces significant proteomic alterations in tumor microenvironments.
- The observed changes in cytoskeletal and iron metabolism proteins may represent a common response pathway to different cancer treatments, including radiotherapy.
