Skip to main content
NCBI home page
The American Journal of Pathology logoLink to The American Journal of Pathology
. 1988 Nov;133(2):374–380.

Human squamous carcinoma cells express complex defects in the control of proliferation and differentiation.

R E Scott 1, M S Wilke 1, J J Wille Jr 1, M R Pittelkow 1, B M Hsu 1, J L Kasperbauer 1
PMCID: PMC1880781  PMID: 3056022

Abstract

Four human squamous carcinoma cell (SCC) lines (SCC-9, SCC-13, SCC-15, and SCC-25) were studied to characterize their relative ability to control proliferation and differentiation. These experiments were based on previous data that established that in normal human keratinocytes three distinct and sequential steps are involved in the integrated control of proliferation and differentiation: 1) reversible growth-arrest at a predifferentiation state, 2) irreversible loss of proliferative potential, and 3) terminal differentiation. The current results show that SCC can show changes in the culture conditions required to undergo reversible growth-arrest and SCC can express partial or complete defects in their ability to irreversibly growth-arrest or terminally differentiate. For example, SCC-9 and SCC-25 cannot irreversibly growth-arrest or terminally differentiate, SCC-13 can irreversibly growth-arrest but cannot terminally differentiate, and SCC-15 can irreversibly growth-arrest and terminally differentiate to a moderate extent. These results therefore extend previous data by establishing that the malignant transformation of human epithelial cells does not simply result from defects in the control of terminal differentiation but rather from a combination of complex defects in the regulation of proliferation and differentiation.

Full text

PDF
374

Selected References

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

  1. Breitkreutz D., Hornung J., Pöhlmann J., Brown-Bierman L., Bohnert A., Bowden P. E., Fusenig N. E. Environmental induction of differentiation-specific keratins in malignant mouse keratinocyte lines. Eur J Cell Biol. 1986 Dec;42(2):255–267. [PubMed] [Google Scholar]
  2. Chen T. R. In situ detection of mycoplasma contamination in cell cultures by fluorescent Hoechst 33258 stain. Exp Cell Res. 1977 Feb;104(2):255–262. doi: 10.1016/0014-4827(77)90089-1. [DOI] [PubMed] [Google Scholar]
  3. Green H. Terminal differentiation of cultured human epidermal cells. Cell. 1977 Jun;11(2):405–416. doi: 10.1016/0092-8674(77)90058-7. [DOI] [PubMed] [Google Scholar]
  4. Holley R. W., Kiernan J. A. "Contact inhibition" of cell division in 3T3 cells. Proc Natl Acad Sci U S A. 1968 May;60(1):300–304. doi: 10.1073/pnas.60.1.300. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Lechner J. F., McClendon I. A., LaVeck M. A., Shamsuddin A. M., Harris C. C. Differential control by platelet factors of squamous differentiation in normal and malignant human bronchial epithelial cells. Cancer Res. 1983 Dec;43(12 Pt 1):5915–5921. [PubMed] [Google Scholar]
  6. Pierce G. B. Differentiation of normal and malignant cells. Fed Proc. 1970 May-Jun;29(3):1248–1254. [PubMed] [Google Scholar]
  7. Pittelkow M. R., Scott R. E. New techniques for the in vitro culture of human skin keratinocytes and perspectives on their use for grafting of patients with extensive burns. Mayo Clin Proc. 1986 Oct;61(10):771–777. doi: 10.1016/s0025-6196(12)64815-0. [DOI] [PubMed] [Google Scholar]
  8. Pittelkow M. R., Wille J. J., Jr, Scott R. E. Two functionally distinct classes of growth arrest states in human prokeratinocytes that regulate clonogenic potential. J Invest Dermatol. 1986 Apr;86(4):410–417. doi: 10.1111/1523-1747.ep12285684. [DOI] [PubMed] [Google Scholar]
  9. Rheinwald J. G., Beckett M. A. Defective terminal differentiation in culture as a consistent and selectable character of malignant human keratinocytes. Cell. 1980 Nov;22(2 Pt 2):629–632. doi: 10.1016/0092-8674(80)90373-6. [DOI] [PubMed] [Google Scholar]
  10. Rhim J. S., Jay G., Arnstein P., Price F. M., Sanford K. K., Aaronson S. A. Neoplastic transformation of human epidermal keratinocytes by AD12-SV40 and Kirsten sarcoma viruses. Science. 1985 Mar 8;227(4691):1250–1252. doi: 10.1126/science.2579430. [DOI] [PubMed] [Google Scholar]
  11. Sachs L. Constitutive uncoupling of pathways of gene expression that control growth and differentiation in myeloid leukemia: a model for the origin and progression of malignancy. Proc Natl Acad Sci U S A. 1980 Oct;77(10):6152–6156. doi: 10.1073/pnas.77.10.6152. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Shipley G. D., Pittelkow M. R., Wille J. J., Jr, Scott R. E., Moses H. L. Reversible inhibition of normal human prokeratinocyte proliferation by type beta transforming growth factor-growth inhibitor in serum-free medium. Cancer Res. 1986 Apr;46(4 Pt 2):2068–2071. [PubMed] [Google Scholar]
  13. Sporn M. B., Roberts A. B. Autocrine growth factors and cancer. 1985 Feb 28-Mar 6Nature. 313(6005):745–747. doi: 10.1038/313745a0. [DOI] [PubMed] [Google Scholar]
  14. Steinberg M. L., Defendi V. Altered pattern of growth and differentiation in human keratinocytes infected by simian virus 40. Proc Natl Acad Sci U S A. 1979 Feb;76(2):801–805. doi: 10.1073/pnas.76.2.801. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Wilke M. S., Hsu B. M., Wille J. J., Jr, Pittelkow M. R., Scott R. E. Biologic mechanisms for the regulation of normal human keratinocyte proliferation and differentiation. Am J Pathol. 1988 Apr;131(1):171–181. [PMC free article] [PubMed] [Google Scholar]
  16. Wille J. J., Jr, Pittelkow M. R., Scott R. E. Normal and transformed human prokeratinocytes express divergent effects of a tumor promoter on cell cycle-mediated control of proliferation and differentiation. Carcinogenesis. 1985 Aug;6(8):1181–1187. doi: 10.1093/carcin/6.8.1181. [DOI] [PubMed] [Google Scholar]
  17. Wille J. J., Jr, Pittelkow M. R., Shipley G. D., Scott R. E. Integrated control of growth and differentiation of normal human prokeratinocytes cultured in serum-free medium: clonal analyses, growth kinetics, and cell cycle studies. J Cell Physiol. 1984 Oct;121(1):31–44. doi: 10.1002/jcp.1041210106. [DOI] [PubMed] [Google Scholar]
  18. Wille J. J., Jr, Scott R. E. Suppression of tumorigenicity by the cell-cycle-dependent control of cellular differentiation and proliferation. Int J Cancer. 1986 Jun 15;37(6):875–881. doi: 10.1002/ijc.2910370613. [DOI] [PubMed] [Google Scholar]
  19. Yuspa S. H., Morgan D. L. Mouse skin cells resistant to terminal differentiation associated with initiation of carcinogenesis. Nature. 1981 Sep 3;293(5827):72–74. doi: 10.1038/293072a0. [DOI] [PubMed] [Google Scholar]

Articles from The American Journal of Pathology are provided here courtesy of American Society for Investigative Pathology

RESOURCES