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Published on: June 2, 2022
Salmonella reduces tumor metastasis by downregulation C-X-C chemokine receptor type 4
Tai-Huang Lee1, Gaun-You Lin2, Ming-Hui Yang3
1Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Taiwan.
Abstract:
Tumor metastasis is the main reason for the death of most cancer patients. C-X-C chemokine receptor type 4 (CXCR4) has been demonstrated to be overexpressed in numerous types of cancer. CXCR4 selectively binds with stromal cell-derived factor 1 (SDF1), also known as C-X-C family chemokine ligand 12 (CXCL12) (CXCL12/SDF-1), which induced tumor proliferation and metastasis. Recently, the use of conventional cancer treatments had some limitation; bacteria treatment for cancer becomes a trend that overcomes these limitations. Plenty of studies show that Salmonella has anti-tumor and anti-metastatic activity. The current study aimed to investigate Salmonella suppresses CXCR4 protein expression and tumor cell migration ability in B16F10 melanoma and LL2 lung carcinoma cells. Salmonella reduced CXCR4 protein expression through downregulating Protein Kinase-B (Akt)/Mammalian Target of Rapamycin (mTOR) signaling pathway. In cells transfected with constitutively active Akt plasmids, a reverse effect of Salmonella-induced inhibition of CXCR4 was observed. Tumor cells have chemotactic response to CXCL12 in migration assay, and we found that Salmonella reduced tumor chemotactic response after CXCL12 treatment. The C57BL/6 mice were intravenously injected with B16F10 and LL2 cells pre-incubated with or without Salmonella, the tumor size and lung weight of Salmonella group had obviously decreased, indicating anti-metastatic effect that confirmed the findings from the in vitro experiments.
Insights
Salmonella bacteria effectively reduce cancer metastasis by suppressing CXCR4 protein expression and tumor cell migration. This bacterial therapy shows promise in overcoming limitations of conventional cancer treatments.
Area of Science:
- Oncology
- Microbiology
- Molecular Biology
Background:
- Tumor metastasis, driven by C-X-C chemokine receptor type 4 (CXCR4) and its ligand CXCL12, is a primary cause of cancer mortality.
- Conventional cancer treatments face limitations, leading to increased interest in alternative therapies like bacterial treatments.
- Salmonella bacteria exhibit known anti-tumor and anti-metastatic properties.
Purpose of the Study:
- To investigate the potential of Salmonella to suppress CXCR4 protein expression and tumor cell migration in B16F10 melanoma and LL2 lung carcinoma cells.
- To elucidate the molecular mechanisms underlying Salmonella's anti-metastatic effects, specifically focusing on the Akt/mTOR signaling pathway.
Main Methods:
- In vitro experiments assessed CXCR4 protein expression and tumor cell migration in response to Salmonella treatment in B16F10 and LL2 cell lines.
- The role of the Protein Kinase-B (Akt)/Mammalian Target of Rapamycin (mTOR) signaling pathway was investigated using constitutively active Akt plasmids.
- In vivo studies involved injecting C57BL/6 mice with B16F10 and LL2 cells pre-treated with Salmonella to evaluate anti-metastatic effects by measuring tumor size and lung weight.
Main Results:
- Salmonella significantly reduced CXCR4 protein expression in B16F10 and LL2 cells.
- Salmonella downregulated the Akt/mTOR signaling pathway, which was confirmed by the reversal of CXCR4 inhibition in cells with constitutively active Akt.
- Salmonella treatment decreased tumor cell chemotactic response to CXCL12 and significantly reduced tumor size and lung weight in vivo, indicating an anti-metastatic effect.
Conclusions:
- Salmonella possesses anti-metastatic activity against melanoma and lung carcinoma by inhibiting CXCR4 expression and tumor cell migration.
- The anti-metastatic effect of Salmonella is mediated through the downregulation of the Akt/mTOR signaling pathway.
- Salmonella represents a promising therapeutic agent for combating cancer metastasis.
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