Year 2020,
Volume: 4 Issue: 2, 149 - 153, 01.06.2020
Abstract
References
- Ruiz C, Lenkiewicz E, Evers L, et al. Advancing a clinically relevant perspective of the clonal nature of cancer. Proc Natl Acad Sci 2011;108:12054–12059. [CrossRef]
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- Heselmeyer K, Schröck E, Du Manoir S, et al. Gain of chromosome 3q defines the transition from severe dysplasia to invasive carcinoma of the uterine cervix. Proc Natl Acad Sci U S A 1996;93:479–484. [CrossRef]
- Habermann JK, Paulsen U, Roblick UJ, et al. Stage-specific alterations of the genome, transcriptome, and proteome during colorectal carcinogenesis. Genes Chromosomes Cancer 2007;46:10–26. [CrossRef]
- Platzer P, Upender MB, Wilson K, et al. Silence of chromosomal amplifications in colon cancer. Cancer Res 2002;62:1134–1138. https:// cancerres.aacrjournals.org/content/canres/62/4/1134.full.pdf
- Schwendel A, Langreck H, Reichel M, et al. Primary small-cell lung carcinomas and their metastases are characterized by a recurrent pattern of genetic alterations. Int J Cancer 1997;74:86–93. [CrossRef]
- Ghadimi BM, Schröck E, Walker RL, et al. Specific chromosomal aberrations and amplification of the AIB1 nuclear receptor coactivator gene in pancreatic carcinomas. Am J Pathol 1999;154:525–536. [CrossRef]
- Knutsen T, Padilla-Nash HM, Wangsa D, et al. Definitive molecular cytogenetic characterization of 15 colorectal cancer cell lines. Genes Chromosomes Cancer 2010;49:204–223. [CrossRef]
- Ried T, Hu Y, Difilippantonio MJ, Ghadimi BM, Grade M, Camps J. The consequences of chromosomal aneuploidy on the transcriptome of cancer cells. Biochim Biophys Acta 2012;1819:784–793. [CrossRef]
- Upender MB, Habermann JK, McShane LM, et al. Chromosome transfer induced aneuploidy results in complex dysregulation of the cellular transcriptome in immortalized and cancer cells. Cancer Res 2004;64:6941–6949. [CrossRef]
- Chin K, DeVries S, Fridlyand J, et al. Genomic and transcriptional aberrations linked to breast cancer pathophysiologies. Cancer Cell 2006;10:529–541. [CrossRef]
- Neve RM, Chin K, Fridlyand J, et al. A collection of breast cancer cell lines for the study of functionally distinct cancer subtypes. Cancer Cell 2006;10:515–527. [CrossRef]
- Heim S, Mitelman F, editors. Cancer Cytogenetics: Chromosomal and Molecular Genetic Aberrations of Tumor Cells, 4th ed. Wiley- Blackwell; 2015. 648 p. [CrossRef]
- Elegheert J, Behiels E, Bishop B, et al. Lentiviral transduction of mammalian cells for fast, scalable and high-level production of soluble and membrane proteins. Nat Protoc 2018;13:2991–3017. [CrossRef]
- Milone MC, O’Doherty U. Clinical use of lentiviral vectors. Leukemia 2018;32:1529–1541. https://www.nature.com/articles/s41375-018- 0106-0
Generation of an in vitro Intratumoral Heterogeneity Model by Lentiviral Fluorescent Labeling of Colon Cancer Cell Line DLD-1 Subclones
Abstract
Purpose: Studying genomic changes during tumor progression has helped to understand the biology of many different cancers and has been the basis for targeted therapy strategies. However, resistance and differences in response to therapy in patients are still very important issues. One of the major underlying reasons is intratumoral cellular heterogeneity. Clones harbor mutations and/or epigenetic patterns providing a survival advantage under changing micro-environmental conditions are the main culprits of therapy resistance. Therefore, it is crucial to define and to study the properties and the contributions of these deviant subclones in vitro. In order to achieve that, we have generated a fluorescent intratumoral heterogeneity model of the colon cancer cell line DLD-1.Methods: We used 2N subclones C3 and C34 and 4N subclones B9 and B12 of DLD-1, isolated by our team previously. Subclones were stably transduced using lentiviral vectors carrying different fluorescent labels and selected by puromycin.Results: Labeled subclones were mixed in equal proportions and a co-culture model of intratumoral heterogeneity was generated. Fluorescent signals were then confirmed by fluorescence microscope.Conclusion: The in vitro model we have generated may be used in many tumor kinetic studies. By co-culturing different clones, profiles that have a selective advantage under different conditions can be detected. After exposure to different chemotherapeutic agents, radiation and/or combinations, real time changes in population kinetics can be tracked. By comparing these results to the genomic profiling of subclones, it will be possible to relate variations that are responsible for any observed therapeutic resistance in vitro
References
- Ruiz C, Lenkiewicz E, Evers L, et al. Advancing a clinically relevant perspective of the clonal nature of cancer. Proc Natl Acad Sci 2011;108:12054–12059. [CrossRef]
- Nowell PC. The clonal evolution of tumor cell populations. Science 1976;194:23–28.
- Naugler CT. Population genetics of cancer cell clones: possible implications of cancer stem cells. Theor Biol Med Model 2010;7:42. [CrossRef]
- Salk JJ, Fox EJ, Loeb LA. Mutational Heterogeneity in Human Cancers: Origin and Consequences. Annu Rev Pathol 2010;5:51–75. [CrossRef]
- Masramon L, Vendrell E, Tarafa G, et al. Genetic instability and divergence of clonal populations in colon cancer cells in vitro. J Cell Sci 2006;119:1477–1482. [CrossRef]
- Wangsa D, Quintanilla I, Torabi K, et al. Near-tetraploid cancer cells show chromosome instability triggered by replication stress and exhibit enhanced invasiveness. FASEB J 2018;32:3502–3517. [CrossRef]
- Ried T. Homage to Theodor Boveri (1862–1915): Boveri’s theory of cancer as a disease of the chromosomes, and the landscape of genomic imbalances in human carcinomas. Environ Mol Mutagen 2009;50:593–601. [CrossRef]
- Ried T, Heselmeyer-Haddad K, Blegen H, Schröck E, Auer G. Genomic changes defining the genesis, progression, and malignancy potential in solid human tumors: A phenotype/genotype correlation. Genes Chromosomes and Cancer 1999;25:195–204. [CrossRef]
- Beroukhim R, Mermel CH, Porter D, et al. The landscape of somatic copy-number alteration across human cancers. Nature 2010;463:899–905. [CrossRef]
- Ried T, Knutzen R, Steinbeck R, et al. Comparative genomic hybridization reveals a specific pattern of chromosomal gains and losses during the genesis of colorectal tumors. Genes Chromosomes Cancer 1996;15:234–245. [CrossRef]
- Heselmeyer K, Schröck E, Du Manoir S, et al. Gain of chromosome 3q defines the transition from severe dysplasia to invasive carcinoma of the uterine cervix. Proc Natl Acad Sci U S A 1996;93:479–484. [CrossRef]
- Habermann JK, Paulsen U, Roblick UJ, et al. Stage-specific alterations of the genome, transcriptome, and proteome during colorectal carcinogenesis. Genes Chromosomes Cancer 2007;46:10–26. [CrossRef]
- Platzer P, Upender MB, Wilson K, et al. Silence of chromosomal amplifications in colon cancer. Cancer Res 2002;62:1134–1138. https:// cancerres.aacrjournals.org/content/canres/62/4/1134.full.pdf
- Schwendel A, Langreck H, Reichel M, et al. Primary small-cell lung carcinomas and their metastases are characterized by a recurrent pattern of genetic alterations. Int J Cancer 1997;74:86–93. [CrossRef]
- Ghadimi BM, Schröck E, Walker RL, et al. Specific chromosomal aberrations and amplification of the AIB1 nuclear receptor coactivator gene in pancreatic carcinomas. Am J Pathol 1999;154:525–536. [CrossRef]
- Knutsen T, Padilla-Nash HM, Wangsa D, et al. Definitive molecular cytogenetic characterization of 15 colorectal cancer cell lines. Genes Chromosomes Cancer 2010;49:204–223. [CrossRef]
- Ried T, Hu Y, Difilippantonio MJ, Ghadimi BM, Grade M, Camps J. The consequences of chromosomal aneuploidy on the transcriptome of cancer cells. Biochim Biophys Acta 2012;1819:784–793. [CrossRef]
- Upender MB, Habermann JK, McShane LM, et al. Chromosome transfer induced aneuploidy results in complex dysregulation of the cellular transcriptome in immortalized and cancer cells. Cancer Res 2004;64:6941–6949. [CrossRef]
- Chin K, DeVries S, Fridlyand J, et al. Genomic and transcriptional aberrations linked to breast cancer pathophysiologies. Cancer Cell 2006;10:529–541. [CrossRef]
- Neve RM, Chin K, Fridlyand J, et al. A collection of breast cancer cell lines for the study of functionally distinct cancer subtypes. Cancer Cell 2006;10:515–527. [CrossRef]
- Heim S, Mitelman F, editors. Cancer Cytogenetics: Chromosomal and Molecular Genetic Aberrations of Tumor Cells, 4th ed. Wiley- Blackwell; 2015. 648 p. [CrossRef]
- Elegheert J, Behiels E, Bishop B, et al. Lentiviral transduction of mammalian cells for fast, scalable and high-level production of soluble and membrane proteins. Nat Protoc 2018;13:2991–3017. [CrossRef]
- Milone MC, O’Doherty U. Clinical use of lentiviral vectors. Leukemia 2018;32:1529–1541. https://www.nature.com/articles/s41375-018- 0106-0
There are 23 citations in total.
Details
| Primary Language | English |
|---|---|
| Journal Section | Research Article |
| Authors | |
| Publication Date | June 1, 2020 |
| Published in Issue | Year 2020 Volume: 4 Issue: 2 |