EMT, Stemness, and Drug Resistance in Biological Context: A 3D Tumor Tissue/In Silico Platform for Analysis of Combinatorial Treatment in NSCLC with Aggressive KRAS-Biomarker Signatures
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Matrix Preparation
2.2. Cells
2.3. Preparation of Tumor Models
2.4. Patient Tumor Samples
2.5. Treatment of Cells in 2D and 3D
2.6. Stimulation of Cells with hTGF-β1
2.7. Immuno/Histochemical Stainings
2.8. Quantification of Proliferation and Cell Invasion
2.9. M30 ELISA
2.10. Viability Assays (MTT-Test and CellTiter-Glo®)
2.11. Western Blotting
2.12. Statistics
2.13. Lung Cancer PCR Array
2.14. Ultrastructural Analysis
2.15. In Silico 3D Tissue Simulations/Bioinformatics
3. Results
3.1. Generation and Characterization of the 3D Lung Cancer Tissue Model
3.2. Assessment of EMT, Differentiation, Stemness, and Invasion
3.3. EMT Correlation with Drug Response
3.4. Set-Up of Combined In Vitro/In Silico Models with KRAS Signatures
3.5. TGF-β1-Induced EMT Does Not Mediate Resistance toward Targeted Therapies
3.6. EMT Status and CD44 Expression Are No Predictors of Drug Response in PDX Cell Lines
3.7. Combination Strategies to Overcome Resistance in HCC44 Tumor Models
4. Discussion
4.1. D Tissue Models for More Realistic Preclinical Testing
4.2. EMT Correlation to Drug Resistance and Invasion
4.3. An In Vivo/In Silico Platform for Testing Targeted Therapies
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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Peindl, M.; Göttlich, C.; Crouch, S.; Hoff, N.; Lüttgens, T.; Schmitt, F.; Pereira, J.G.N.; May, C.; Schliermann, A.; Kronenthaler, C.; et al. EMT, Stemness, and Drug Resistance in Biological Context: A 3D Tumor Tissue/In Silico Platform for Analysis of Combinatorial Treatment in NSCLC with Aggressive KRAS-Biomarker Signatures. Cancers 2022, 14, 2176. https://doi.org/10.3390/cancers14092176
Peindl M, Göttlich C, Crouch S, Hoff N, Lüttgens T, Schmitt F, Pereira JGN, May C, Schliermann A, Kronenthaler C, et al. EMT, Stemness, and Drug Resistance in Biological Context: A 3D Tumor Tissue/In Silico Platform for Analysis of Combinatorial Treatment in NSCLC with Aggressive KRAS-Biomarker Signatures. Cancers. 2022; 14(9):2176. https://doi.org/10.3390/cancers14092176
Chicago/Turabian StylePeindl, Matthias, Claudia Göttlich, Samantha Crouch, Niklas Hoff, Tamara Lüttgens, Franziska Schmitt, Jesús Guillermo Nieves Pereira, Celina May, Anna Schliermann, Corinna Kronenthaler, and et al. 2022. "EMT, Stemness, and Drug Resistance in Biological Context: A 3D Tumor Tissue/In Silico Platform for Analysis of Combinatorial Treatment in NSCLC with Aggressive KRAS-Biomarker Signatures" Cancers 14, no. 9: 2176. https://doi.org/10.3390/cancers14092176