Comprehensive Mutational and Phenotypic Characterization of New Metastatic Cutaneous Squamous Cell Carcinoma Cell Lines Reveal Novel Drug Susceptibilities
Abstract
:1. Introduction
2. Results
2.1. Phenotypic Validation of Novel Cell Lines from Patients with Metastatic cSCC
2.2. Genotypic Validation of Novel Cell Lines from Patients with Metastatic cSCC
2.3. Effect of In Vitro Culture on Cancer Gene Expression Patterns
2.4. High-Throughput and Secondary Drug Screens Reveal Novel Therapeutic Targets in Metastatic cSCC Cell Lines
3. Discussion
4. Materials and Methods
4.1. Patient Characteristics and Specimen Selection
4.2. Cell Culture Development and Maintenance
4.3. Generation of Mouse Xenografts
4.4. Organotypic Invasion Assay
4.5. Nucleic Acid Extraction
4.6. Gene Expression Analysis
4.7. Whole-Genome Sequencing (WGS) and Bioinformatics Analysis Pipeline
4.8. Chemical Compound Library Assays and Analysis
4.9. Secondary Dose-Response Screening
4.10. Cell Lysate Preparation and Western Blot Analysis
4.11. Data Repository
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
cSCC | Cutaneous squamous cell carcinoma |
NER | Nuclear excision repair |
SNV | Small nucleotide variant |
UV | Ultraviolet radiation |
WGS | Whole genome sequencing |
References
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Compound | Drug Class | UW-CSCC1 | UW-CSCC1-R | UW-CSCC2 |
---|---|---|---|---|
IC50 µM | ||||
Dactosilib | Dual PI3K/mTOR inhibitor | 0.022 ± 0.003 | 0.080 ± 0.023 | 0.028 ± 0.012 |
PIK-75 | PI3K inhibitor | 0.122 ± 0.012 | 0.204 ± 0.05 | 0.026 ± 0.012 |
5-Fluorouracil | Antimetabolite | 4.47 ± 0.4 | 7.56 ± 0.1 | - |
Carboplatin † | Platinum analogue | 22.40 | 22.90 | 200.00 |
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Perry, J.; Ashford, B.; Thind, A.S.; Gauthier, M.-E.; Minaei, E.; Major, G.; Iyer, N.G.; Gupta, R.; Clark, J.; Ranson, M. Comprehensive Mutational and Phenotypic Characterization of New Metastatic Cutaneous Squamous Cell Carcinoma Cell Lines Reveal Novel Drug Susceptibilities. Int. J. Mol. Sci. 2020, 21, 9536. https://doi.org/10.3390/ijms21249536
Perry J, Ashford B, Thind AS, Gauthier M-E, Minaei E, Major G, Iyer NG, Gupta R, Clark J, Ranson M. Comprehensive Mutational and Phenotypic Characterization of New Metastatic Cutaneous Squamous Cell Carcinoma Cell Lines Reveal Novel Drug Susceptibilities. International Journal of Molecular Sciences. 2020; 21(24):9536. https://doi.org/10.3390/ijms21249536
Chicago/Turabian StylePerry, Jay, Bruce Ashford, Amarinder Singh Thind, Marie-Emilie Gauthier, Elahe Minaei, Gretel Major, Narayanan Gopalakrishna Iyer, Ruta Gupta, Jonathan Clark, and Marie Ranson. 2020. "Comprehensive Mutational and Phenotypic Characterization of New Metastatic Cutaneous Squamous Cell Carcinoma Cell Lines Reveal Novel Drug Susceptibilities" International Journal of Molecular Sciences 21, no. 24: 9536. https://doi.org/10.3390/ijms21249536