Multidimensional phenotyping of breast cancer cell lines to guide preclinical research

Purpose Cell lines are extremely useful tools in breast cancer research. Their key benefits include a high degree of control over experimental variables and reproducibility. However, the advantages must be balanced against the limitations of modelling such a complex disease in vitro. Informed select...

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Published in:	Breast cancer research and treatment 2018, Vol.167 (1), p.289-301
Main Authors:	Saunus, Jodi M., Smart, Chanel E., Kutasovic, Jamie R., Johnston, Rebecca L., Kalita-de Croft, Priyakshi, Miranda, Mariska, Rozali, Esdy N., Vargas, Ana Cristina, Reid, Lynne E., Lorsy, Eva, Cocciardi, Sibylle, Seidens, Tatjana, McCart Reed, Amy E., Dalley, Andrew J., Wockner, Leesa F., Johnson, Julie, Sarkar, Debina, Askarian-Amiri, Marjan E., Simpson, Peter T., Khanna, Kum Kum, Chenevix-Trench, Georgia, Al-Ejeh, Fares, Lakhani, Sunil R.
Format:	Article
Language:	eng
Subjects:	1-Phosphatidylinositol 3-kinase Breast cancer Breast Neoplasms - genetics Brief Report Cancer Cancer research CD44 antigen Cell culture Cell Line, Tumor E-cadherin Epidermal growth factor receptors ErbB-2 protein Female Flow Cytometry Gene Expression Profiling Gene Expression Regulation, Neoplastic - genetics Genetic Heterogeneity Genotype Genotypes Humans Immunohistochemistry Knowledge Medical research Medicine Medicine & Public Health Mutation Neoplasm Proteins - genetics Oncology Oncology, Experimental p53 Protein Phenotype Phenotypes Phenotyping Ribonucleic acid RNA Transforming growth factor-b Transforming growth factors Tumor cell lines Tumor proteins Vimentin Xenografts
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Summary:	Purpose Cell lines are extremely useful tools in breast cancer research. Their key benefits include a high degree of control over experimental variables and reproducibility. However, the advantages must be balanced against the limitations of modelling such a complex disease in vitro. Informed selection of cell line(s) for a given experiment now requires essential knowledge about molecular and phenotypic context in the culture dish. Methods We performed multidimensional profiling of 36 widely used breast cancer cell lines that were cultured under standardised conditions. Flow cytometry and digital immunohistochemistry were used to compare the expression of 14 classical breast cancer biomarkers related to intrinsic molecular profiles and differentiation states: EpCAM, CD24, CD49f, CD44, ER, AR, HER2, EGFR, E-cadherin, p53, vimentin, and cytokeratins 5, 8/18 and 19. Results This cell-by-cell analysis revealed striking heterogeneity within cultures of individual lines that would be otherwise obscured by analysing cell homogenates, particularly amongst the triple-negative lines. High levels of p53 protein, but not RNA, were associated with somatic mutations ( p = 0.008). We also identified new subgroups using the nanoString PanCancer Pathways panel (730 transcripts representing 13 canonical cancer pathways). Unsupervised clustering identified five groups: luminal/HER2, immortalised (‘normal’), claudin-low and two basal clusters, distinguished mostly by baseline expression of TGF-beta and PI3-kinase pathway genes. Conclusion These features are compared with other published genotype and phenotype information in a user-friendly reference table to help guide selection of the most appropriate models for in vitro and in vivo studies, and as a framework for classifying new patient-derived cancer cell lines and xenografts.
ISSN:	0167-6806 1573-7217