Prostate Cancer’s Silent Partners: Fibroblasts and Their Influence on Glutamine Metabolism Manipulation
Abstract
:1. Introduction
2. Results
2.1. Established Prostate Cancer Cell Lines Expressing mKATE2-NLS to Trace Cell Proliferation and Clonogenic Potential
2.2. Cancer-Associated Fibroblasts Sensitise the Hormone-Sensitive LNCaPcell Line to Glutamine Deprivation
2.3. Cancer-Associated Fibroblasts Reprogram LNCaP Cell’s Metabolic Needs
2.4. Cancer-Associated Fibroblasts Reduce the Inhibitory Effect of CB839 on Clonogenic Potential
2.5. Low GLS1 Expression in Stroma and High Expression in Epithelial Cells Is a Marker for Bad Prognosis
3. Discussion
4. Materials and Methods
4.1. Cell Lines
4.2. Lentivirus Production, eGFP-NLS and mKATE2-NLS Nuclei Labelling, and Image Cytometry
4.3. Gln Deprivation and CB-839 Treatment
4.4. Proliferation Assay with the IncuCyte® S3 Live-Cell Analysis System
4.5. Clonogenic Assay
4.6. Western Blot
4.7. Data Preparation, Imputation, Overrepresentation Analysis (ORA), and Gene Set Enrichment Analysis (GSEA) of the Mass Spectrometry Data
4.8. Patients and Study Design
4.9. Immunohistochemistry
4.10. qPCR
4.11. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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All | HSPC | CRPC | |
---|---|---|---|
Patient Number | 108 | 26 | 82 |
Median age at primary diagnosis, years | 71 | 72 | 71 |
Median PSA at primary diagnosis, ng/mL (Interquartile range IQR) | 17 | 6.3 | 32.5 |
(6.8; 73.0) | (2.7; 10.2) | (8.9; 101.6) | |
Neuroendocrine differentiation at primary diagnosis, % | 1 | 0 | 1 |
Presence of bone metastases at primary diagnosis, % | 25 | 3.8 | 32 |
Presence of lymph node metastases at primary diagnosis, % | 14 | 12 | 11.7 |
Presence of organ metastases at primary diagnosis, % | 1 | 1 | 1 |
Median overall survival since the start of primary therapy, months | 59 | 47 | 81 |
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Hönscheid, P.V.; Baretton, G.B.; Puhr, M.; Siciliano, T.; Israel, J.S.; Stope, M.B.; Ebersbach, C.; Beier, A.-M.K.; Thomas, C.; Erb, H.H.H. Prostate Cancer’s Silent Partners: Fibroblasts and Their Influence on Glutamine Metabolism Manipulation. Int. J. Mol. Sci. 2024, 25, 9275. https://doi.org/10.3390/ijms25179275
Hönscheid PV, Baretton GB, Puhr M, Siciliano T, Israel JS, Stope MB, Ebersbach C, Beier A-MK, Thomas C, Erb HHH. Prostate Cancer’s Silent Partners: Fibroblasts and Their Influence on Glutamine Metabolism Manipulation. International Journal of Molecular Sciences. 2024; 25(17):9275. https://doi.org/10.3390/ijms25179275
Chicago/Turabian StyleHönscheid, Pia V., Gustavo B. Baretton, Martin Puhr, Tiziana Siciliano, Justus S. Israel, Matthias B. Stope, Celina Ebersbach, Alicia-Marie K. Beier, Christian Thomas, and Holger H. H. Erb. 2024. "Prostate Cancer’s Silent Partners: Fibroblasts and Their Influence on Glutamine Metabolism Manipulation" International Journal of Molecular Sciences 25, no. 17: 9275. https://doi.org/10.3390/ijms25179275