The LIFR Inhibitor EC359 Effectively Targets Type II Endometrial Cancer by Blocking LIF/LIFR Oncogenic Signaling
Abstract
:1. Introduction
2. Results
2.1. Type II ECa Patients Express Higher Levels of LIF
2.2. Functional LIFR Is Needed for Optimal Growth of Type II ECa Cells
2.3. EC359 Reduced the Cell Viability, Survival, and Invasion of Patient-Derived and Established Type II ECa Cells
2.4. EC359 Induced Apoptosis and Inhibited the Growth of Patient-Derived Organoids (PDOs)
2.5. EC359 Reduced LIFR Downstream Signaling in Type II ECa Cells
2.6. EC359 Reduced Patient-Derived Xenograft (PDX) Tumor Growth In Vivo
3. Discussion
4. Materials and Methods
4.1. Cell Culture and Reagents
4.2. Primary Type II Endometrial Cancer Cells
4.3. Generation of LIFR-Knockdown Cells
4.4. Cell Viability Assays
4.5. Clonogenic Survival Assays
4.6. Cell Invasion Assays
4.7. Apoptosis Assays
4.8. Reporter Gene Assays
4.9. Western Blotting and RT-qPCR
4.10. Patient-Derived Organoid (PDO) Studies
4.11. In Vivo Patient-Derived Xenograft (PDX) Models and Immunohistochemistry (IHC)
4.12. Statistical Analysis
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Number | Histology | Grade |
---|---|---|
ECa-4 | Serous Papillary | Grade 3 |
ECa-6 | Serous Papillary | Grade 3 |
ECa-15 | Carcinosarcoma-assoc serous papillary carcinoma | Grade 3 |
ECa-24 | Endometrioid & Serous | Grade 3 |
ECa-47 | Serous papillary carcinoma | Grade 3 |
ECa-66 | Serous papillary endometrial cancer | Grade 3 |
ECa-78 | Clear Cell | Grade 3 |
ECa-81 | Carcinosarcoma | Grade 3 |
ECa-97 | Carcinosarcoma | Grade 3 |
ECa-99 | Carcinosarcoma | Grade 3 |
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Spencer, N.; Rodriguez Sanchez, A.L.; Gopalam, R.; Subbarayalu, P.; Medina, D.M.; Yang, X.; Ramirez, P.; Randolph, L.; Aller, E.J.; Santhamma, B.; et al. The LIFR Inhibitor EC359 Effectively Targets Type II Endometrial Cancer by Blocking LIF/LIFR Oncogenic Signaling. Int. J. Mol. Sci. 2023, 24, 17426. https://doi.org/10.3390/ijms242417426
Spencer N, Rodriguez Sanchez AL, Gopalam R, Subbarayalu P, Medina DM, Yang X, Ramirez P, Randolph L, Aller EJ, Santhamma B, et al. The LIFR Inhibitor EC359 Effectively Targets Type II Endometrial Cancer by Blocking LIF/LIFR Oncogenic Signaling. International Journal of Molecular Sciences. 2023; 24(24):17426. https://doi.org/10.3390/ijms242417426
Chicago/Turabian StyleSpencer, Nicole, Alondra Lee Rodriguez Sanchez, Rahul Gopalam, Panneerdoss Subbarayalu, Daisy M. Medina, Xue Yang, Paulina Ramirez, Lois Randolph, Emily Jean Aller, Bindu Santhamma, and et al. 2023. "The LIFR Inhibitor EC359 Effectively Targets Type II Endometrial Cancer by Blocking LIF/LIFR Oncogenic Signaling" International Journal of Molecular Sciences 24, no. 24: 17426. https://doi.org/10.3390/ijms242417426