Blockade of IL-10 Signaling Ensures Mifamurtide Efficacy in Metastatic Osteosarcoma
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Study Design
2.2. Cell Culture
2.3. Co-Culture and Treatment
2.4. Measurement of Intracellular and Mitochondrial ROS
2.5. Flow Cytometric Analysis
2.6. Real-Time PCR
2.7. ELISA and AlphaLISA Assay
2.8. Luminex Cytokines Quantification
2.9. In Vivo Lung Retention Assay
2.10. Statistical Analysis
3. Results
3.1. Mifamurtide Is Unable to Exert Its Antitumoral Action in the Most Aggressive Osteosarcoma Cell Lines
3.2. Mifamurtide Triggers MAPK and STAT3 Signaling Pathways Only in Macrophages Co-cultured with the Less Aggressive MG-63 Cells
3.3. IL-6 and IL-10 Are Differentially Secreted in Macrophages-Tumor Co-Culture Medium Depending on OS Cell Aggressiveness
3.4. Mifamurtide Treatment Causes a Different Trend of IL-10/IL-6 Ratio on OS Cell Lines Depending on the Different Stage of Malignancy
3.5. An Anti-IL-10 Blocking Antibody Triggers the Anti-Tumoral Activity of Mifamurtide on Aggressive OS Cells
3.6. IL-10 Blocking Antibody Converts the Pro-Tumoral IL-10 Cellular Response into a Tumoricidal Action That Synergize with Mifamurtide
3.7. Administration of Anti-IL-10 Blocking Antibody Synergizes with Mifamurtide in Decreasing Lung Metastasis Dissemination in a Syngeneic OS Model In Vivo
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Correction Statement
References
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Cytokine | ALIVE | DEAD |
---|---|---|
Low IL-6 | n = 12 | n = 0 |
High IL-6 | n = 4 | n = 8 |
Low IL-10 | n = 12 | n = 0 |
High IL-10 | n = 4 | n = 8 |
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Nastasi, N.; Pasha, A.; Bruno, G.; Subbiani, A.; Pietrovito, L.; Leo, A.; Scala, L.; de Simone, L.; Casazza, G.; Lunardi, F.; et al. Blockade of IL-10 Signaling Ensures Mifamurtide Efficacy in Metastatic Osteosarcoma. Cancers 2023, 15, 4744. https://doi.org/10.3390/cancers15194744
Nastasi N, Pasha A, Bruno G, Subbiani A, Pietrovito L, Leo A, Scala L, de Simone L, Casazza G, Lunardi F, et al. Blockade of IL-10 Signaling Ensures Mifamurtide Efficacy in Metastatic Osteosarcoma. Cancers. 2023; 15(19):4744. https://doi.org/10.3390/cancers15194744
Chicago/Turabian StyleNastasi, Nicoletta, Amada Pasha, Gennaro Bruno, Angela Subbiani, Laura Pietrovito, Angela Leo, Lucia Scala, Lorena de Simone, Gabriella Casazza, Federica Lunardi, and et al. 2023. "Blockade of IL-10 Signaling Ensures Mifamurtide Efficacy in Metastatic Osteosarcoma" Cancers 15, no. 19: 4744. https://doi.org/10.3390/cancers15194744
APA StyleNastasi, N., Pasha, A., Bruno, G., Subbiani, A., Pietrovito, L., Leo, A., Scala, L., de Simone, L., Casazza, G., Lunardi, F., Taddei, M. L., Tamburini, A., Tondo, A., Favre, C., & Calvani, M. (2023). Blockade of IL-10 Signaling Ensures Mifamurtide Efficacy in Metastatic Osteosarcoma. Cancers, 15(19), 4744. https://doi.org/10.3390/cancers15194744