Chemoresistant Cancer Cell Lines Are Characterized by Migratory, Amino Acid Metabolism, Protein Catabolism and IFN1 Signalling Perturbations
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Cell Culture
2.2. Primary HGSOC Culture
2.3. In Vitro Motility Assay
2.4. Chick Chorioallantoic Membrane (CAM) Assay
2.5. Cell Survival Assay
2.6. Metabolomics Sample Preparation
2.7. Metabolomics Data Acquisition
2.8. Metabolomics Data Analysis
2.9. Metabolomic Functional Pathway Analysis
2.10. Cell Lysis and Acetone Precipitation
2.11. Tryptophan Fluorescence Assay for Protein Estimation
2.12. Protein Digestion and Clean Up
2.13. Proteomics Data Acquisition
2.14. Proteomics Data Analysis
2.15. Functional Annotation of Biological Process
2.16. KEGG Global Metabolomic Network Analysis of Metabolites and Proteins of Interest
2.17. Kaplan Meier Analysis
3. Results
3.1. Generation and Growth Rate of CBPR Cells
3.2. OVCAR-5 CBPR Cells Are More Motile than OVCAR-5 Parental In Vitro
3.3. OVCAR-5 Cells Are More Invasive in the In Vivo CAM Assay
3.4. LC-MSMS Analysis of Metabolites in Resistant vs. Parental Ovarian Cancer Cell Lines
3.5. Classification of Ovarian Cancer Cell Lines Based on Metabolomic Profiles
3.6. LC-MSMS Analysis of Proteins in Resistant vs. Parental Ovarian Cancer Cell Lines
3.7. Separation of Ovarian Cancer Cell Lines Based on Proteomic Profiles
3.8. Functional Analysis of Differentially Abundant Proteins between Parental and CBPR Cancer Cell Lines
3.9. KEGG Global Metabolomic Network Analysis of Differentially Abundant Proteins and Metabolites between Parental and CBPR Cell Lines
3.10. Kaplan Meier Analysis of Proteins of Interest in Chemoresistance
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Rank | Term | Count | Involved Genes/Total Genes (%) | p-Value |
---|---|---|---|---|
1 | cytoskeleton organisation | 29 | 13.1 | 3.2 × 10−0.4 |
2 | antigen processing and presentation of peptide antigen | 10 | 4.5 | 3.5 × 10−0.4 |
3 | cellular component assembly | 51 | 23 | 6.3 × 10−0.4 |
4 | response to cytokine | 22 | 9.9 | 8.1 × 10−0.4 |
5 | cell junction organisation | 11 | 5 | 9.8 × 10−0.4 |
6 | cytokine-mediated signalling pathway | 17 | 7.7 | 1.3 × 10−0.3 |
7 | intermediate filament cytoskeleton organisation | 5 | 2.3 | 1.7 × 10−0.3 |
8 | regulation of cellular component organisation | 45 | 20.3 | 1.7 × 10−0.3 |
9 | type I interferon signalling pathway | 6 | 2.7 | 2.1 × 10−0.3 |
10 | cell junction assembly | 9 | 4.1 | 2.5 × 10−0.3 |
Rank | Term | Count | Involved Genes/Total Genes (%) | p-Value |
---|---|---|---|---|
1 | negative regulation of necroptotic process | 3 | 2.2 | 1.8 × 10−0.3 |
2 | response to type I interferon | 5 | 3.7 | 2.5 × 10−0.3 |
3 | cellular macromolecule catabolic process | 16 | 11.9 | 4.8 × 10−0.3 |
4 | negative regulation of cellular protein metabolic process | 16 | 11.9 | 5.5 × 10−0.3 |
5 | protein catabolic process | 14 | 10.4 | 6.1 × 10−0.3 |
6 | positive regulation of extrinsic apoptotic signalling pathway | 4 | 3 | 7.1 × 10−0.3 |
7 | intermediate filament organisation | 3 | 2.2 | 1.0 × 10−0.2 |
8 | response to cytokine | 13 | 9.7 | 1.4 × 10−0.2 |
9 | regulation of protein ubiquitination | 7 | 5.2 | 1.0 × 10−0.2 |
10 | positive regulation of proteolysis | 8 | 6 | 1.60 × 10−0.2 |
Rank | Metabolite Set | Count (Metabolites) | Count (Proteins) | Count (Total) | p-Value |
---|---|---|---|---|---|
1 | Alanine, aspartate and glutamate metabolism | 4 | 2 | 6 | 0.0000817 |
2 | Glycolysis/Gluconeogenesis | 2 | 3 | 5 | 0.000717 |
3 | Pyruvate metabolism | 2 | 3 | 5 | 0.00419 |
4 | Inositol phosphate metabolism | 0 | 4 | 4 | 0.0053 |
5 | Arginine and proline metabolism | 3 | 1 | 4 | 0.0189 |
6 | Citrate cycle (TCA cycle) | 2 | 1 | 3 | 0.0208 |
7 | Limonene and pinene degradation | 1 | 0 | 1 | 0.03 |
8 | Chloroalkane and chloroalkene degradation | 1 | 1 | 2 | 0.0348 |
9 | Valine, leucine and isoleucine degradation | 2 | 1 | 3 | 0.0445 |
10 | Fatty acid biosynthesis | 0 | 2 | 2 | 0.0452 |
Rank | Metabolite Set | Count (Metabolites) | Count (Proteins) | Count (Total) | p-Value |
---|---|---|---|---|---|
1 | Alanine, aspartate and glutamate metabolism | 2 | 1 | 3 | 0.00692 |
2 | Arginine and proline metabolism | 1 | 2 | 3 | 0.0148 |
3 | Folate biosynthesis | 0 | 2 | 2 | 0.045 |
4 | Linoleic acid metabolism | 0 | 1 | 1 | 0.0858 |
5 | Vitamin B6 metabolism | 1 | 0 | 1 | 0.0893 |
6 | Glycine, serine and threonine metabolism | 2 | 0 | 2 | 0.0895 |
7 | Glycosylphosphatidylinositol (GPI)-anchor biosynthesis | 0 | 1 | 1 | 0.134 |
8 | Thiamine metabolism | 0 | 1 | 1 | 0.145 |
9 | Amino sugar and nucleotide sugar metabolism | 0 | 2 | 2 | 0.145 |
10 | Sphingolipid metabolism | 0 | 1 | 1 | 0.181 |
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Acland, M.; Lokman, N.A.; Young, C.; Anderson, D.; Condina, M.; Desire, C.; Noye, T.M.; Wang, W.; Ricciardelli, C.; Creek, D.J.; et al. Chemoresistant Cancer Cell Lines Are Characterized by Migratory, Amino Acid Metabolism, Protein Catabolism and IFN1 Signalling Perturbations. Cancers 2022, 14, 2763. https://doi.org/10.3390/cancers14112763
Acland M, Lokman NA, Young C, Anderson D, Condina M, Desire C, Noye TM, Wang W, Ricciardelli C, Creek DJ, et al. Chemoresistant Cancer Cell Lines Are Characterized by Migratory, Amino Acid Metabolism, Protein Catabolism and IFN1 Signalling Perturbations. Cancers. 2022; 14(11):2763. https://doi.org/10.3390/cancers14112763
Chicago/Turabian StyleAcland, Mitchell, Noor A. Lokman, Clifford Young, Dovile Anderson, Mark Condina, Chris Desire, Tannith M. Noye, Wanqi Wang, Carmela Ricciardelli, Darren J. Creek, and et al. 2022. "Chemoresistant Cancer Cell Lines Are Characterized by Migratory, Amino Acid Metabolism, Protein Catabolism and IFN1 Signalling Perturbations" Cancers 14, no. 11: 2763. https://doi.org/10.3390/cancers14112763