Cancer cell lines are used in many biomedical research laboratories. Why, then, are they often described as unrepresentative of the cells from which they were derived? Here, I argue that they have been unjustly accused. Under the right conditions, and with appropriate controls, properly authenticated cancer cell lines retain the properties of the cancers of origin.
Subscribe to Journal
Get full journal access for 1 year
only $21.58 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
O'Hare, M. J. in Human Cancer in Primary Culture (ed. Masters, J. R. W.) 271– 286 (Kluwer Academic, Dordrecht, 1991).
Hsu, M.-Y., Elder, D. A. & Herlyn, M. in Human Cell Culture Volume 1, Cancer Cell Lines Part 1 (eds Masters, J. R. W. & Palsson, B.) 259– 274 (Kluwer Academic, Dordrecht, 1999).
Lansford, C. D. et al. in Human Cell Culture Volume 2, Cancer Cell Lines Part 2 (eds Masters, J. R. W. & Palsson, B.) 185–255 (Kluwer Academic, Dordrecht, 1999).
Fogh, J., Fogh, J. M. & Orfeo, T. One hundred and twenty-seven cultured human tumour cell lines producing tumours in nude mice. J. Natl Cancer Inst. 59, 221–226 (1977).
Wistuba, I. I. et al. Comparison of features of human breast cancer cell lines and their corresponding tumours. Clin. Cancer Res. 4, 2931–2938 (1998).
Wistuba, I. I. et al. Comparison of features of human lung cancer cell lines and their corresponding tumours. Clin. Cancer Res. 5, 991–1000 (1999).
Drexler, H. G. Review of alterations of the cyclin-dependent kinase inhibitor INK4 family genes p15, p16, p18 and p19 in human leukemia-lymphoma cells. Leukemia 12, 845–859 ( 1998).
Drexler, H. G. et al. p53 alterations in human leukemia-lymphoma cell lines: in vitro artefact or prerequisite for cell immortalization? Leukemia 14, 198–206 ( 2000).
Ross, D. T. et al. Systematic variation in gene expression patterns in human cancer cell lines. Nature Genet. 24, 227 –235 (2000).
Walker, M. C., Parris, C. N. & Masters, J. R. W. Differential sensitivities to chemotherapeutic drugs between testicular and bladder cancer cells. J. Natl Cancer Inst 79, 213–216 ( 1987).
Knuechel, R. & Masters, J. R. W. in Human Cell Culture Volume 1, Cancer Cell Lines Part 1 (eds Masters, J. R. W. & Palsson, B.) 213–230 (Kluwer Academic, Dordrecht, 1999).
UKCCCR guidelines for the use of cell lines in cancer research. Br. J. Cancer 82, 1495– 1509 (2000).
Dirks, W. G., MacLeod, R. A. F. & Drexler, H. G. ECV304 (endothelial) is really T24 (bladder carcinoma): cell line cross-contamination at source. In Vitro Cell Dev. Biol. Anim. 35, 558–559 ( 1999).
Gartler, S. M. Genetic markers as tracers in cell culture. Natl Cancer Inst. Monogr. 26, 167–195 ( 1967).
Gold, M. A Conspiracy of Cells. One Woman's Immortal Legacy and the Scandal It Caused (State University of New York, Albany, 1986).
Nelson-Rees, W. A., Flandermeyer, R. R. & Hawthorne, P. K. Banded marker chromosomes as indicators of intraspecies cellular contamination. Science 184, 1093 (1974).
Nelson-Rees, W. A., Daniels, D. W. & Flandermeyer, R. R. Cross-contamination of cells in culture. Science 212, 446–452 ( 1981).
Gey, G. O., Coffman, W. D. & Kubicek, M. T. Tissue culture studies of the proliferative capacity of cervical carcinoma and normal epithelium. Cancer Res. 12, 264–265 (1952).
Markovic, O. & Markovic, N. Cell cross-contamination in cell cultures: the silent and neglected danger. In Vitro Cell Dev. Biol. Anim. 34, 1–8 ( 1998).
MacLeod, R. A. F. et al. Widespread intraspecies cross-contamination of human tumour cell lines. Int. J. Cancer 83, 555– 563 (1999).
MacLeod, R. A. F. & Drexler, H. G. in Human Cell Culture Volume 3, Leukemias and Lymphomas (eds Masters, J. R. W. & Palsson, B.) 373–399 (Kluwer Academic, Dordrecht, 2000).
Povey, S., Hopkinson, D. A., Harris, H. & Franks, L. M. Characterisation of human cell lines and differentiation from HeLa by enzyme typing. Nature 264, 60– 63 (1976).
O'Toole, C. M., Povey, S., Hepburn, P. & Franks, L. M. Identity of some human bladder cancer cell lines. Nature 301, 429–430 (1981).
Gilbert, D. A. et al. Application of DNA fingerprints for cell line individualization . Am. J. Hum. Genet. 47, 499– 514 (1990).
Freshney, R. I. Culture of Animal Cells. A Manual of Basic Technique 4th edn (Wiley-Liss, New York, 2000).
Drexler, H. G. & Uphoff, C. C. in The Encyclopedia of Cell Technology (eds Spier, R. E., Griffiths E. & Scragg, A. H.) 609–627 (Wiley, New York, 2000).
Hay, R. J., Macy, M. L. & Chen, T. R. Mycoplasma infection of cultured cells. Nature 339, 487–499 ( 1989).
Virmani, A. K. et al. Promoter methylation and silencing of the retinoic acid receptor-β gene in lung carcinomas. J. Natl Cancer Inst. 92, 1303–1307 (2000).
Virmani, A. K. et al. Allelotyping demonstrates common and distinct patterns of chromosomal loss in human lung cancer types. Genes Chrom. Cancer 21, 308–319 ( 1998).
Shivapurkar, N. et al. Multiple regions of chromosome 4 demonstrating allelic losses in breast carcinomas. Cancer Res. 59, 3576 –3580 (1999).
Masters, J. R. W. & Lakhani, S. How microarrays can help cancer patients. Nature 404, 921 (2000).
Alizadeh, A. A. et al. Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature 403, 503–511 (2000).
Schaeffer, W. I. Usage of vertebrate, invertebrate and plant cell, tissue and organ culture terminology. In vitro 20, 19– 24 (1984).
Jat, P. S. & Sharp, P. A. Cell lines established by a temperature-sensitive simian virus 40 large-T-antigen are growth restricted at the nonpermissive temperature. Mol. Cell. Biol. 9, 1672– 1681 (1989).
Stamps, A. C., Davies, S. C., Burman, J. & O'Hare, M. J. Analysis of proviral integration in human mammary epithelial cell lines immortalized by retroviral infection with a temperature-sensitive SV40 T-antigen construct . Int. J. Cancer 57, 865– 874 (1994).
Simon, L. V., Beauchamp, J. R., O'Hare, M. & Olsen, I. Establishment of long-term myogenic cultures from patients with Duchenne muscular dystrophy by retroviral transduction of a temperature-sensitive SV40 large T antigen. Exp. Cell Res. 224, 264– 271 (1996).
Thomson, J. A., Pilotti, V., Stevens, P., Ayres, K. L. & Debenham, P. G. Validation of short tandem repeat analysis for the investigation of cases of disputed paternity. Forensic Sci. Int. 100, 1–16 ( 1999).
I thank Alan Entwistle, Ludwig Institute for Cancer Research, University College London for help preparing the time-lapse movies and Jim Thomson, Laboratory of the Government Chemist, London, UK for providing images for Figure 1.
Video time lapse of five frequently used human cancer cell lines, collected at 15 frames per hour with a x20 objective. The frame represents an area of 627 micrometres by 470 micrometres. Features to notice include the ruffled membranes at the leading edge of the cells and dividing cells. There is relatively little cell movement. The cell lines are:
HeLa (cervix) (MPG 1169 kb)
Images collected by Alan Entwistle (Ludwig Institute for Cancer Research, Royal Free and UCL Branch) and John Masters.
About this article
Trends in Cancer (2020)
BMC Medical Genomics (2020)
A Sub-Clone of RAW264.7-Cells Form Osteoclast-Like Cells Capable of Bone Resorption Faster than Parental RAW264.7 through Increased De Novo Expression and Nuclear Translocation of NFATc1
International Journal of Molecular Sciences (2020)
Genetic Alterations Featuring Biological Models to Tailor Clinical Management of Pancreatic Cancer Patients
Investigative Opthalmology & Visual Science (2020)