c-Met Mediated Cytokine Network Promotes Brain Metastasis of Breast Cancer by Remodeling Neutrophil Activities
Abstract
:Simple Summary
Abstract
1. Introduction
2. Material and Methods
2.1. Human Samples
2.2. Cell Culture and Reagents
2.3. Tissue Culture Conditions
2.4. Plasmids and Reagents
2.5. Conditioned Medium (CM) Preparation
2.6. Neutrophil Isolation
2.7. Immunohistochemistry
2.8. ELISA Assays
2.9. Quantitative Real-Time PCR
2.10. Animal Experiments
2.11. Flow Cytometry
2.12. Neutrophil Migration Assay
2.13. Mammary Sphere Formation Assay
2.14. Tube Formation Assay
2.15. RNA Sequencing
2.16. Cohort Analysis
2.17. Statistical Analysis
3. Results
3.1. c-Met Expression in Tumor Cells Is Associated with the Enrichment of Neutrophils in Brain Metastatic Sites
3.2. c-Met Pathway Promotes the Release of a Group of Neutrophil-Related Cytokines
3.3. CM of Brain Metastatic Cells Regulates Neutrophil Activities in a c-Met Dependent Manner
3.4. Depletion of Neutrophils Suppresses Brain Metastasis In Vivo
3.5. Phenotypic Switch of Neutrophils Is Associated with c-Met Signaling in Tumor Cells
3.6. Neutrophils Promote Cancer Cell Stemness through LCN2
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Liu, Y.; Smith, M.R.; Wang, Y.; D’Agostino, R., Jr.; Ruiz, J.; Lycan, T.; Kucera, G.L.; Miller, L.D.; Li, W.; Chan, M.D.; et al. c-Met Mediated Cytokine Network Promotes Brain Metastasis of Breast Cancer by Remodeling Neutrophil Activities. Cancers 2023, 15, 2626. https://doi.org/10.3390/cancers15092626
Liu Y, Smith MR, Wang Y, D’Agostino R Jr., Ruiz J, Lycan T, Kucera GL, Miller LD, Li W, Chan MD, et al. c-Met Mediated Cytokine Network Promotes Brain Metastasis of Breast Cancer by Remodeling Neutrophil Activities. Cancers. 2023; 15(9):2626. https://doi.org/10.3390/cancers15092626
Chicago/Turabian StyleLiu, Yin, Margaret R. Smith, Yuezhu Wang, Ralph D’Agostino, Jr., Jimmy Ruiz, Thomas Lycan, Gregory L. Kucera, Lance D. Miller, Wencheng Li, Michael D. Chan, and et al. 2023. "c-Met Mediated Cytokine Network Promotes Brain Metastasis of Breast Cancer by Remodeling Neutrophil Activities" Cancers 15, no. 9: 2626. https://doi.org/10.3390/cancers15092626