Human cancer cell lines: fact and fantasy


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.

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Figure 1: DNA profiling of short tandem repeats.


  1. 1

    O'Hare, M. J. in Human Cancer in Primary Culture (ed. Masters, J. R. W.) 271– 286 (Kluwer Academic, Dordrecht, 1991).

    Google Scholar 

  2. 2

    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).

    Google Scholar 

  3. 3

    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).

    Google Scholar 

  4. 4

    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).

    CAS  Article  Google Scholar 

  5. 5

    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).

    CAS  PubMed  Google Scholar 

  6. 6

    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).

    CAS  PubMed  Google Scholar 

  7. 7

    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).

    CAS  Article  Google Scholar 

  8. 8

    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).

    CAS  Article  Google Scholar 

  9. 9

    Ross, D. T. et al. Systematic variation in gene expression patterns in human cancer cell lines. Nature Genet. 24, 227 –235 (2000).

    CAS  Article  Google Scholar 

  10. 10

    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).

    CAS  PubMed  Google Scholar 

  11. 11

    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).

    Google Scholar 

  12. 12

    UKCCCR guidelines for the use of cell lines in cancer research. Br. J. Cancer 82, 1495– 1509 (2000).

  13. 13

    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).

    CAS  Article  Google Scholar 

  14. 14

    Gartler, S. M. Genetic markers as tracers in cell culture. Natl Cancer Inst. Monogr. 26, 167–195 ( 1967).

    CAS  PubMed  Google Scholar 

  15. 15

    Gold, M. A Conspiracy of Cells. One Woman's Immortal Legacy and the Scandal It Caused (State University of New York, Albany, 1986).

    Google Scholar 

  16. 16

    Nelson-Rees, W. A., Flandermeyer, R. R. & Hawthorne, P. K. Banded marker chromosomes as indicators of intraspecies cellular contamination. Science 184, 1093 (1974).

    CAS  Article  Google Scholar 

  17. 17

    Nelson-Rees, W. A., Daniels, D. W. & Flandermeyer, R. R. Cross-contamination of cells in culture. Science 212, 446–452 ( 1981).

    CAS  Article  Google Scholar 

  18. 18

    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).

    Google Scholar 

  19. 19

    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).

    CAS  Article  Google Scholar 

  20. 20

    MacLeod, R. A. F. et al. Widespread intraspecies cross-contamination of human tumour cell lines. Int. J. Cancer 83, 555– 563 (1999).

    CAS  Article  Google Scholar 

  21. 21

    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).

    Google Scholar 

  22. 22

    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).

    CAS  Article  Google Scholar 

  23. 23

    O'Toole, C. M., Povey, S., Hepburn, P. & Franks, L. M. Identity of some human bladder cancer cell lines. Nature 301, 429–430 (1981).

    Article  Google Scholar 

  24. 24

    Gilbert, D. A. et al. Application of DNA fingerprints for cell line individualization . Am. J. Hum. Genet. 47, 499– 514 (1990).

    CAS  PubMed  PubMed Central  Google Scholar 

  25. 25

    Freshney, R. I. Culture of Animal Cells. A Manual of Basic Technique 4th edn (Wiley-Liss, New York, 2000).

    Google Scholar 

  26. 26

    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).

    Google Scholar 

  27. 27

    Hay, R. J., Macy, M. L. & Chen, T. R. Mycoplasma infection of cultured cells. Nature 339, 487–499 ( 1989).

    CAS  Article  Google Scholar 

  28. 28

    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).

    CAS  Article  Google Scholar 

  29. 29

    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).

    CAS  Article  Google Scholar 

  30. 30

    Shivapurkar, N. et al. Multiple regions of chromosome 4 demonstrating allelic losses in breast carcinomas. Cancer Res. 59, 3576 –3580 (1999).

    CAS  PubMed  Google Scholar 

  31. 31

    Masters, J. R. W. & Lakhani, S. How microarrays can help cancer patients. Nature 404, 921 (2000).

    CAS  Article  Google Scholar 

  32. 32

    Alizadeh, A. A. et al. Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature 403, 503–511 (2000).

    CAS  Article  Google Scholar 

  33. 33

    Schaeffer, W. I. Usage of vertebrate, invertebrate and plant cell, tissue and organ culture terminology. In vitro 20, 19– 24 (1984).

    CAS  Article  Google Scholar 

  34. 34

    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).

    CAS  Article  Google Scholar 

  35. 35

    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).

    CAS  Article  Google Scholar 

  36. 36

    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).

    CAS  Article  Google Scholar 

  37. 37

    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).

    CAS  Article  Google Scholar 

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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.

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German Collection of Microorganisms and Cell Cultures

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Masters, J. Human cancer cell lines: fact and fantasy. Nat Rev Mol Cell Biol 1, 233–236 (2000).

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