<i>Salmonella</i> Impacts Tumor-Induced Macrophage Polarization, and Inhibits SNAI1-Mediated Metastasis in Melanoma
Targeting metastasis is a vital strategy to improve the clinical outcome of cancer patients, specifically in cases with high-grade malignancies. Here, we employed a <i>Salmonella</i>-based treatment to address metastasis. The potential of <i>Salmonella</i> as an anticancer ag...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-06-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/12/2894 |
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| author | Christian R. Pangilinan Li-Hsien Wu Che-Hsin Lee |
| author_facet | Christian R. Pangilinan Li-Hsien Wu Che-Hsin Lee |
| author_sort | Christian R. Pangilinan |
| collection | DOAJ |
| description | Targeting metastasis is a vital strategy to improve the clinical outcome of cancer patients, specifically in cases with high-grade malignancies. Here, we employed a <i>Salmonella</i>-based treatment to address metastasis. The potential of <i>Salmonella</i> as an anticancer agent has been extensively studied; however, the mechanism through which it affects metastasis remains unclear. This study found that the epithelial-to-mesenchymal transition (EMT) inducer SNAI1 was markedly reduced in <i>Salmonella</i>-treated melanoma cells, as revealed by immunoblotting. Furthermore, wound healing and transwell assays showed a reduced in vitro cell migration following <i>Salmonella</i> treatment. Transfection experiments confirmed that <i>Salmonella</i> acted against metastasis by suppressing protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling, which in turn inhibited SNAI1 expression. Since it is known that metastasis is also influenced by inflammation, we partly characterized the immune infiltrates in melanoma as affected by <i>Salmonella</i> treatment. We found through tumor-macrophage co-culture that <i>Salmonella</i> treatment increased high mobility group box 1 (HMGB1) secretion in tumors to coax the polarization of macrophages in favor of an M1-like phenotype, as shown by increased inducible nitric oxide synthase (iNOS) expression and Interleukin 1 Beta (IL-1<i>β</i>) secretion. Data from our animal study corroborated the in vitro findings, wherein the <i>Salmonella</i>-treated group obtained the lowest lung metastases, longer survival, and increased iNOS-expressing immune infiltrates. |
| first_indexed | 2024-03-10T10:32:56Z |
| format | Article |
| id | doaj.art-257c95e682fa41428da93cef3f39cd63 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T10:32:56Z |
| publishDate | 2021-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-257c95e682fa41428da93cef3f39cd632023-11-21T23:27:51ZengMDPI AGCancers2072-66942021-06-011312289410.3390/cancers13122894<i>Salmonella</i> Impacts Tumor-Induced Macrophage Polarization, and Inhibits SNAI1-Mediated Metastasis in MelanomaChristian R. Pangilinan0Li-Hsien Wu1Che-Hsin Lee2Department of Biological Sciences, National Sun Yat-sen University, Kaohsiung 80424, TaiwanDepartment of Biological Sciences, National Sun Yat-sen University, Kaohsiung 80424, TaiwanDepartment of Biological Sciences, National Sun Yat-sen University, Kaohsiung 80424, TaiwanTargeting metastasis is a vital strategy to improve the clinical outcome of cancer patients, specifically in cases with high-grade malignancies. Here, we employed a <i>Salmonella</i>-based treatment to address metastasis. The potential of <i>Salmonella</i> as an anticancer agent has been extensively studied; however, the mechanism through which it affects metastasis remains unclear. This study found that the epithelial-to-mesenchymal transition (EMT) inducer SNAI1 was markedly reduced in <i>Salmonella</i>-treated melanoma cells, as revealed by immunoblotting. Furthermore, wound healing and transwell assays showed a reduced in vitro cell migration following <i>Salmonella</i> treatment. Transfection experiments confirmed that <i>Salmonella</i> acted against metastasis by suppressing protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling, which in turn inhibited SNAI1 expression. Since it is known that metastasis is also influenced by inflammation, we partly characterized the immune infiltrates in melanoma as affected by <i>Salmonella</i> treatment. We found through tumor-macrophage co-culture that <i>Salmonella</i> treatment increased high mobility group box 1 (HMGB1) secretion in tumors to coax the polarization of macrophages in favor of an M1-like phenotype, as shown by increased inducible nitric oxide synthase (iNOS) expression and Interleukin 1 Beta (IL-1<i>β</i>) secretion. Data from our animal study corroborated the in vitro findings, wherein the <i>Salmonella</i>-treated group obtained the lowest lung metastases, longer survival, and increased iNOS-expressing immune infiltrates.https://www.mdpi.com/2072-6694/13/12/2894<i>Salmonella</i>-mediated tumor therapymelanomametastasismacrophage polarization |
| spellingShingle | Christian R. Pangilinan Li-Hsien Wu Che-Hsin Lee <i>Salmonella</i> Impacts Tumor-Induced Macrophage Polarization, and Inhibits SNAI1-Mediated Metastasis in Melanoma Cancers <i>Salmonella</i>-mediated tumor therapy melanoma metastasis macrophage polarization |
| title | <i>Salmonella</i> Impacts Tumor-Induced Macrophage Polarization, and Inhibits SNAI1-Mediated Metastasis in Melanoma |
| title_full | <i>Salmonella</i> Impacts Tumor-Induced Macrophage Polarization, and Inhibits SNAI1-Mediated Metastasis in Melanoma |
| title_fullStr | <i>Salmonella</i> Impacts Tumor-Induced Macrophage Polarization, and Inhibits SNAI1-Mediated Metastasis in Melanoma |
| title_full_unstemmed | <i>Salmonella</i> Impacts Tumor-Induced Macrophage Polarization, and Inhibits SNAI1-Mediated Metastasis in Melanoma |
| title_short | <i>Salmonella</i> Impacts Tumor-Induced Macrophage Polarization, and Inhibits SNAI1-Mediated Metastasis in Melanoma |
| title_sort | i salmonella i impacts tumor induced macrophage polarization and inhibits snai1 mediated metastasis in melanoma |
| topic | <i>Salmonella</i>-mediated tumor therapy melanoma metastasis macrophage polarization |
| url | https://www.mdpi.com/2072-6694/13/12/2894 |
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