Density-dependent inhibition of fibroblast growth is overcome by pure mitogenic factors


CELL density is of interest because it may have a critical role in the regulation of growth, development, and in malignant transformation. In cell culture, crowding slows and eventually stops cell proliferation of a variety of cells maintained on a solid surface1–5. This property is usually lost after malignant transformation1–5. Two major hypotheses have evolved to explain this phenomenon. The contact inhibition hypothesis holds that specific surface receptors are activated by cell–cell contact and generate a negative signal which halts further growth1–3. The humoral hypothesis proposes that high cell density limits the availability of medium components, particularly of growth factors present in serum4,5. Although much experimental evidence has been adduced in support of the humoral hypothesis, most experiments in which the effect of cell density on growth has been thoroughly investigated were performed in the presence of whole serum as the source of growth factors. The chemical complexity of serum leaves open the possibility that some of its effects may be exerted by molecules that interfere with inhibitory cell–cell contacts. Thus, definitive evidence for a humoral hypothesis in growth regulation in culture is still lacking. To circumvent this objection we have examined the effect of cell density in a model system in which chemically defined molecules rather than whole serum stimulate DNA synthesis and cell division in sparse or crowded cells arrested in G0/G1. We report here that density dependent inhibition of fibroblast growth is overcome by pure mitogenic factors.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.


  1. 1

    Dulbecco, R. in Growth Control in Cell Cultures (eds Wolstenholm, G. E. W. & Knight, J.) 71 (Churchill Livingstone, Edinburgh and London, 1971).

  2. 2

    Noonan, K. D. & Burger, M. M. Prog. Surf. Membr. Sci. 8, 245 (1974).

  3. 3

    Westermark, B. Biochem. biophys. Res. Commun. 69, 304 (1976).

  4. 4

    Holley, R. W. Nature 258, 487 (1975).

  5. 5

    Rozengurt, E. in Eukaryotic Cell Function and Growth (eds Dumont, J. E., Brown, B. L. & Marshall, N. J.) 711 (Plenum, New York, 1976).

  6. 6

    Mierzejewski, K. & Rosengurt, E. Biochem. biophys. Res. Commun. 73, 271 (1976).

  7. 7

    Huang, D. & Cuatrecasas, P. J. cell. Biol. 250, 8251 (1975).

  8. 8

    Rubin, H. Proc. natn. Acad. Sci. U.S.A. 69, 712 (1972).

  9. 9

    Todaro, G. J. & De. Larco, J. E. Nature 264, 26 (1976).

  10. 10

    Bourne, H. R. & Rozengurt, E. Proc. natn. Acad. Sci. U.S.A. 73, 4555 (1976).

Download references

Author information



Rights and permissions

Reprints and Permissions

About this article

Cite this article

MIERZEJEWSKI, K., ROZENGURT, E. Density-dependent inhibition of fibroblast growth is overcome by pure mitogenic factors. Nature 269, 155–156 (1977).

Download citation

Further reading


By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.