Mycobacterium indicus pranii therapy suppresses systemic dissemination of tumor cells in B16F10 murine model of melanoma
Cancer associated morbidity is mostly attributed to the dissemination of tumor cells from their primary niche into the circulation known as “metastasis”. Mycobacterium indicus pranii (MIP) an approved immunotherapeutic agent against lung cancer (NSCLC) has shown potent anti-tumor activity in prior s...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-04-01
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| Series: | Biomedicine & Pharmacotherapy |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0753332223000951 |
| _version_ | 1797894757055201280 |
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| author | Anush Chakraborty Gargi Roy Farheen Fatima Bharati Swami Sangeeta Bhaskar |
| author_facet | Anush Chakraborty Gargi Roy Farheen Fatima Bharati Swami Sangeeta Bhaskar |
| author_sort | Anush Chakraborty |
| collection | DOAJ |
| description | Cancer associated morbidity is mostly attributed to the dissemination of tumor cells from their primary niche into the circulation known as “metastasis”. Mycobacterium indicus pranii (MIP) an approved immunotherapeutic agent against lung cancer (NSCLC) has shown potent anti-tumor activity in prior studies. While evaluating anti-tumor activity of MIP in mouse model, MIP treated animals typically exhibited less metastatic lesions in their pulmonary compartment. To study the role of MIP in metastasis closely, B16F10 melanoma cells were implanted subcutaneously in the mice, and the dissemination of tumor cells from the solid tumor was evaluated over a period of time. When B16F10 melanoma cells were treated with MIP in vitro, downregulation of epithelial mesenchymal transition markers was observed in these cells, which in turn suppressed the invasion, migration and adhesion of tumor cells. Notably, MIP therapy was found to be effectively reducing the metastatic burden in murine model of melanoma. Molecular characterization of MIP treated tumor cells substantiated that MIP upregulates the PPARγ expression within the tumor cells, which attenuates the NFκB/p65 levels within the nucleus, resulting in the suppression of Mmp9 expression in tumor cells. Besides that, MIP also downregulated the surface expression of chemokine receptor CXCR4 in murine melanoma cells, where chromatin immunoprecipitation confirmed the impeded recruitment of p50 and c-Rel factors to the Cxcr4 promoter, resulting in its downregulation transcriptionally. Taken together, MIP suppressed the dissemination of tumor cells in vivo, by regulating the expression of MMP9 and CXCR4 on these cells. |
| first_indexed | 2024-04-10T07:14:24Z |
| format | Article |
| id | doaj.art-bd336672fbc04c3289668a50049841c1 |
| institution | Directory Open Access Journal |
| issn | 0753-3322 |
| language | English |
| last_indexed | 2024-04-10T07:14:24Z |
| publishDate | 2023-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biomedicine & Pharmacotherapy |
| spelling | doaj.art-bd336672fbc04c3289668a50049841c12023-02-26T04:26:22ZengElsevierBiomedicine & Pharmacotherapy0753-33222023-04-01160114307Mycobacterium indicus pranii therapy suppresses systemic dissemination of tumor cells in B16F10 murine model of melanomaAnush Chakraborty0Gargi Roy1Farheen Fatima2Bharati Swami3Sangeeta Bhaskar4Product Development Cell-I, National Institute of Immunology, New Delhi, IndiaProduct Development Cell-I, National Institute of Immunology, New Delhi, IndiaProduct Development Cell-I, National Institute of Immunology, New Delhi, IndiaProduct Development Cell-I, National Institute of Immunology, New Delhi, IndiaCorresponding author.; Product Development Cell-I, National Institute of Immunology, New Delhi, IndiaCancer associated morbidity is mostly attributed to the dissemination of tumor cells from their primary niche into the circulation known as “metastasis”. Mycobacterium indicus pranii (MIP) an approved immunotherapeutic agent against lung cancer (NSCLC) has shown potent anti-tumor activity in prior studies. While evaluating anti-tumor activity of MIP in mouse model, MIP treated animals typically exhibited less metastatic lesions in their pulmonary compartment. To study the role of MIP in metastasis closely, B16F10 melanoma cells were implanted subcutaneously in the mice, and the dissemination of tumor cells from the solid tumor was evaluated over a period of time. When B16F10 melanoma cells were treated with MIP in vitro, downregulation of epithelial mesenchymal transition markers was observed in these cells, which in turn suppressed the invasion, migration and adhesion of tumor cells. Notably, MIP therapy was found to be effectively reducing the metastatic burden in murine model of melanoma. Molecular characterization of MIP treated tumor cells substantiated that MIP upregulates the PPARγ expression within the tumor cells, which attenuates the NFκB/p65 levels within the nucleus, resulting in the suppression of Mmp9 expression in tumor cells. Besides that, MIP also downregulated the surface expression of chemokine receptor CXCR4 in murine melanoma cells, where chromatin immunoprecipitation confirmed the impeded recruitment of p50 and c-Rel factors to the Cxcr4 promoter, resulting in its downregulation transcriptionally. Taken together, MIP suppressed the dissemination of tumor cells in vivo, by regulating the expression of MMP9 and CXCR4 on these cells.http://www.sciencedirect.com/science/article/pii/S0753332223000951Mycobacterium indicus praniiMetastasisCancer immunotherapyMmp9CXCR4 |
| spellingShingle | Anush Chakraborty Gargi Roy Farheen Fatima Bharati Swami Sangeeta Bhaskar Mycobacterium indicus pranii therapy suppresses systemic dissemination of tumor cells in B16F10 murine model of melanoma Biomedicine & Pharmacotherapy Mycobacterium indicus pranii Metastasis Cancer immunotherapy Mmp9 CXCR4 |
| title | Mycobacterium indicus pranii therapy suppresses systemic dissemination of tumor cells in B16F10 murine model of melanoma |
| title_full | Mycobacterium indicus pranii therapy suppresses systemic dissemination of tumor cells in B16F10 murine model of melanoma |
| title_fullStr | Mycobacterium indicus pranii therapy suppresses systemic dissemination of tumor cells in B16F10 murine model of melanoma |
| title_full_unstemmed | Mycobacterium indicus pranii therapy suppresses systemic dissemination of tumor cells in B16F10 murine model of melanoma |
| title_short | Mycobacterium indicus pranii therapy suppresses systemic dissemination of tumor cells in B16F10 murine model of melanoma |
| title_sort | mycobacterium indicus pranii therapy suppresses systemic dissemination of tumor cells in b16f10 murine model of melanoma |
| topic | Mycobacterium indicus pranii Metastasis Cancer immunotherapy Mmp9 CXCR4 |
| url | http://www.sciencedirect.com/science/article/pii/S0753332223000951 |
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