Mycobacterium indicus pranii therapy suppresses systemic dissemination of tumor cells in B16F10 murine model of melanoma

• Published in: Biomedicine & pharmacotherapy 2023-04, Vol.160, p.114307-114307, Article 114307
• Main Authors: Chakraborty, Anush, Roy, Gargi, Fatima, Farheen, Swami, Bharati, Bhaskar, Sangeeta
• Format: Article
• Language: English
• Subjects: Animals; Cancer immunotherapy; CXCR4; Disease Models, Animal; Matrix Metalloproteinase 9; Melanoma - therapy; Metastasis; Mice; Mmp9; Mycobacterium; Mycobacterium indicus pranii
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2023.114307

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. [Display omitted] MIP therapy reduced metastasis of B16F10 cells from primary tumor.Mmp9 is downregulated by MIP therapy in a PPARγ dependent manner in tumor cells.MIP therapy significantly reduced the surface expression of CXCR4 on tumor cells.c-Rel and p50 recruitment to Cxcr4 promoter is suppressed in MIP treated tumor cells.MIP and AMD3100 in combination obliterated metastasis completely in murine tumor.