Inhibiting Endothelial Cell Function in Normal and Tumor Angiogenesis Using BMP Type I Receptor Macrocyclic Kinase Inhibitors
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Cell Culture
2.2. Reagents
2.3. Luciferase Reporter Assay
2.4. Western Blot Analysis
2.5. Quantitative Reverse Transcription PCR (RT-qPCR)
2.6. Kinase Profiling Assay
2.7. Biochemical Affinity Assessment
2.8. Migration Assay
2.9. Proliferation Assay
2.10. MTS Assay
2.11. Cord Formation Assay
2.12. Chemotactic Invasion Assay
2.13. Zebrafish Embryo Toxicity Assay
2.14. Zebrafish Dorsal Longitudinal Anastomotic Vessel (DLAV) and Intra Segmental Vessel (ISV) Formation
2.15. Zebrafish Subintestinal Vessel (SIV) Formation
2.16. Tumor Angiogenesis in Zebrafish
2.17. Statistical Analyses
3. Results
3.1. Identification of Two Novel Macrocyclic Compounds as BMPRI Inhibitors
3.2. OD16 and OD29 Specifically Inhibit BMP, but Not TGF-β Signaling
3.3. OD29 Antagonizes VEGF-Induced ERK MAP Kinase
3.4. OD16 and OD29 Antagonize ECS Migration, Cord Formation, and Invasion
3.5. The Macrocyclic OD16 and OD29 Inhibit DLAV, ISV, and SIV Formation in Zebrafish
3.6. OD16 and OD29 Inhibit Breast Cancer-Induced Vessel Invasion in Zebrafish
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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Ma, J.; Ren, J.; Thorikay, M.; van Dinther, M.; Sanchez-Duffhues, G.; Caradec, J.; Benderitter, P.; Hoflack, J.; ten Dijke, P. Inhibiting Endothelial Cell Function in Normal and Tumor Angiogenesis Using BMP Type I Receptor Macrocyclic Kinase Inhibitors. Cancers 2021, 13, 2951. https://doi.org/10.3390/cancers13122951
Ma J, Ren J, Thorikay M, van Dinther M, Sanchez-Duffhues G, Caradec J, Benderitter P, Hoflack J, ten Dijke P. Inhibiting Endothelial Cell Function in Normal and Tumor Angiogenesis Using BMP Type I Receptor Macrocyclic Kinase Inhibitors. Cancers. 2021; 13(12):2951. https://doi.org/10.3390/cancers13122951
Chicago/Turabian StyleMa, Jin, Jiang Ren, Midory Thorikay, Maarten van Dinther, Gonzalo Sanchez-Duffhues, Josselin Caradec, Pascal Benderitter, Jan Hoflack, and Peter ten Dijke. 2021. "Inhibiting Endothelial Cell Function in Normal and Tumor Angiogenesis Using BMP Type I Receptor Macrocyclic Kinase Inhibitors" Cancers 13, no. 12: 2951. https://doi.org/10.3390/cancers13122951