Cellular heterogeneity in tumours (original) (raw)

Abstract

Malignant tumours contain normal cells, descendants of transformed cells, and conceivably also initiated cells which have taken some but not all of the steps toward malignancy, and hybrid cells. Tumours are propagated by multiplication of clonogenic cells, which are a subclass of the descendants of transformed cells. The clonogenic cells of a tumour may differ in respect of morphology, karyotype, metastatic capacity, sensitivity to cytotoxic drugs, expression of cell surface antigens and hormone receptors, immunogenicity, sensitivity to the immune reaction of the host, and other properties. Evidence (disputed by some) suggests that selection of particular subpopulations plays a role in tumour metastasis and recurrence. Heterogeneity may be due to pleoclonal origin, generation of phenotypic diversity within a clone, or spontaneous hybridization and chromosome loss. The possibility of interaction between different subpopulations must be taken into account in discussing tumour cell population kinetics. Heterogeneity also has important therapeutic implications and may help to explain the failure of some therapeutic regimes and the success of others.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Albino A. P., Lloyd K. O., Houghton A. N., Oettgen H. F., Old L. J. Heterogeneity in surface antigen and glycoprotein expression of cell lines derived from different melanoma metastases of the same patient. Implications for the study of tumor antigens. J Exp Med. 1981 Dec 1;154(6):1764–1778. doi: 10.1084/jem.154.6.1764. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Ashall F., Bramwell M. E., Harris H. A new marker for human cancer cells. 1 The Ca antigen and the Ca1 antibody. Lancet. 1982 Jul 3;2(8288):1–6. doi: 10.1016/s0140-6736(82)91150-3. [DOI] [PubMed] [Google Scholar]
  3. Barranco S. C., Ho D. H., Drewinko B., Romsdahl M. M., Humphrey R. M. Differential sensitivites of human melanoma cells grown in vitro to arabinosylcytosine. Cancer Res. 1972 Dec;32(12):2733–2736. [PubMed] [Google Scholar]
  4. Berranco S. C., Drewinko B., Humphrey R. M. Differential response by human melanoma cells to 1,3-bis-(2-chloroethyl)-1-nitrosourea and bleomycin. Mutat Res. 1973 Aug;19(2):277–280. doi: 10.1016/0027-5107(73)90089-4. [DOI] [PubMed] [Google Scholar]
  5. Bodenham D. C. A study of 650 observed malignant melanomas in the South-West region. Ann R Coll Surg Engl. 1968 Oct;43(4):218–239. [PMC free article] [PubMed] [Google Scholar]
  6. Byers V. S., Johnston J. O. Antigenic differences among osteogenic sarcoma tumor cells taken from different locations in human tumors. Cancer Res. 1977 Sep;37(9):3173–3183. [PubMed] [Google Scholar]
  7. Chow D. A., Greenberg A. H. The generation of tumor heterogeneity in vivo. Int J Cancer. 1980 Feb 15;25(2):261–265. doi: 10.1002/ijc.2910250214. [DOI] [PubMed] [Google Scholar]
  8. Dexter D. L., Kowalski H. M., Blazar B. A., Fligiel Z., Vogel R., Heppner G. H. Heterogeneity of tumor cells from a single mouse mammary tumor. Cancer Res. 1978 Oct;38(10):3174–3181. [PubMed] [Google Scholar]
  9. Donelli M. G., Colombo T., Broggini M., Garattini S. Differential distribution of antitumor agents in primary and secondary tumors. Cancer Treat Rep. 1977 Oct;61(7):1319–1324. [PubMed] [Google Scholar]
  10. Fialkow P. J. Clonal origin of human tumors. Biochim Biophys Acta. 1976 Oct 12;458(3):283–321. doi: 10.1016/0304-419x(76)90003-2. [DOI] [PubMed] [Google Scholar]
  11. Fidler I. J., Gruys E., Cifone M. A., Barnes Z., Bucana C. Demonstration of multiple phenotypic diversity in a murine melanoma of recent origin. J Natl Cancer Inst. 1981 Oct;67(4):947–956. [PubMed] [Google Scholar]
  12. Fidler I. J., Hart I. R. Biological diversity in metastatic neoplasms: origins and implications. Science. 1982 Sep 10;217(4564):998–1003. doi: 10.1126/science.7112116. [DOI] [PubMed] [Google Scholar]
  13. Fidler I. J., Kripke M. L. Metastasis results from preexisting variant cells within a malignant tumor. Science. 1977 Aug 26;197(4306):893–895. doi: 10.1126/science.887927. [DOI] [PubMed] [Google Scholar]
  14. Fogel M., Gorelik E., Segal S., Feldman M. Differences in cell surface antigens of tumor metastases and those of the local tumor. J Natl Cancer Inst. 1979 Mar;62(3):585–588. doi: 10.1093/jnci/62.3.585. [DOI] [PubMed] [Google Scholar]
  15. Houghton P. J., Tew K. D., Taylor D. M. Some studies on the distribution and effects of cyclophosphamide (NSC-26271) in normal and neoplastic tissue. Cancer Treat Rep. 1976 Apr;60(4):459–464. [PubMed] [Google Scholar]
  16. Håkansson L., Tropé C. On the presence within tumours of clones that differ in sensitivity to cytostatic drugs. Acta Pathol Microbiol Scand A. 1974 Jan;82(1):35–40. doi: 10.1111/j.1699-0463.1974.tb03825.x. [DOI] [PubMed] [Google Scholar]
  17. Kripke M. L., Gruys E., Fidler I. J. Metastatic heterogeneity of cells from an ultraviolet light-induced murine fibrosarcoma of recent origin. Cancer Res. 1978 Sep;38(9):2962–2967. [PubMed] [Google Scholar]
  18. Lala P. K., Santer V., Rahil K. S. Spontaneous fusion between Ehrlich ascites tumor cells and host cells in vivo: kinetics of hybridization, and concurrent changes in the histocompatiblity profile of the tumor after propagation in different host strains. Eur J Cancer. 1980 Apr;16(4):487–510. doi: 10.1016/0014-2964(80)90229-7. [DOI] [PubMed] [Google Scholar]
  19. McGee J. O., Woods J. C., Ashall F., Bramwell M. E., Harris H. A new marker for human cancer cells, 2 immunohistochemical detection of the Ca antigen in human tissues with the Ca1 antibody. Lancet. 1982 Jul 3;2(8288):7–10. doi: 10.1016/s0140-6736(82)91151-5. [DOI] [PubMed] [Google Scholar]
  20. Miller B. E., Miller F. R., Leith J., Heppner G. H. Growth interaction in vivo between tumor subpopulations derived from a single mouse mammary tumor. Cancer Res. 1980 Nov;40(11):3977–3981. [PubMed] [Google Scholar]
  21. Miller F. R., Heppner G. H. Immunologic heterogeneity of tumor cell subpopulations from a single mouse mammary tumor. J Natl Cancer Inst. 1979 Dec;63(6):1457–1463. [PubMed] [Google Scholar]
  22. Mintz B., Illmensee K. Normal genetically mosaic mice produced from malignant teratocarcinoma cells. Proc Natl Acad Sci U S A. 1975 Sep;72(9):3585–3589. doi: 10.1073/pnas.72.9.3585. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Nowell P. C. The clonal evolution of tumor cell populations. Science. 1976 Oct 1;194(4260):23–28. doi: 10.1126/science.959840. [DOI] [PubMed] [Google Scholar]
  24. Olsson L., Ebbesen P. Natural polyclonality of spontaneous AKR leukemia and its consequences for so-called specific immunotherapy. J Natl Cancer Inst. 1979 Mar;62(3):623–627. doi: 10.1093/jnci/62.3.623. [DOI] [PubMed] [Google Scholar]
  25. Pimm M. V., Baldwin R. W. Antigenic differences between primary methylcholanthrene-induced rat sarcomas and post-surgical recurrences. Int J Cancer. 1977 Jul 15;20(1):37–43. doi: 10.1002/ijc.2910200108. [DOI] [PubMed] [Google Scholar]
  26. Poste G., Doll J., Fidler I. J. Interactions among clonal subpopulations affect stability of the metastatic phenotype in polyclonal populations of B16 melanoma cells. Proc Natl Acad Sci U S A. 1981 Oct;78(10):6226–6230. doi: 10.1073/pnas.78.10.6226. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Poste G., Fidler I. J. The pathogenesis of cancer metastasis. Nature. 1980 Jan 10;283(5743):139–146. doi: 10.1038/283139a0. [DOI] [PubMed] [Google Scholar]
  28. Prehn R. T. Analysis of antigenic heterogeneity within individual 3-methylcholanthrene-induced mouse sarcomas. J Natl Cancer Inst. 1970 Nov;45(5):1039–1045. [PubMed] [Google Scholar]
  29. Reddy A. L., Fialkow P. J. Multicellular origin of fibrosarcomas in mice induced by the chemical carcinogen 3-methylcholanthrene. J Exp Med. 1979 Oct 1;150(4):878–887. doi: 10.1084/jem.150.4.878. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Schmitt M., Daynes R. A. Heterogeneity of tumorigenicity phenotype in murine tumors. I. Characterization of regressor and progressor clones isolated from a nonmutagenized ultraviolet regressor tumor. J Exp Med. 1981 May 1;153(5):1344–1359. doi: 10.1084/jem.153.5.1344. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Sporn M. B., Todaro G. J. Autocrine secretion and malignant transformation of cells. N Engl J Med. 1980 Oct 9;303(15):878–880. doi: 10.1056/NEJM198010093031511. [DOI] [PubMed] [Google Scholar]
  32. Suzuki N., Withers H. R., Koehler M. W. Heterogeneity and variability of artificial lung colony-forming ability among clones from mouse fibrosarcoma. Cancer Res. 1978 Oct;38(10):3349–3351. [PubMed] [Google Scholar]
  33. Tropé C. Different sensitivity to cytostatic drugs of primary tumor and metastasis of the Lewis carcinoma. Neoplasma. 1975;22(2):171–180. [PubMed] [Google Scholar]
  34. Wiener F., Fenyö E. M., Klein G., Harris H. Fusion of tumour cells with host cells. Nat New Biol. 1972 Aug 2;238(83):155–159. doi: 10.1038/newbio238155a0. [DOI] [PubMed] [Google Scholar]
  35. Woodruff M. F., Ansell J. D., Forbes G. M., Gordon J. C., Burton D. I., Micklem H. S. Clonal interaction in tumours. Nature. 1982 Oct 28;299(5886):822–824. doi: 10.1038/299822a0. [DOI] [PubMed] [Google Scholar]