Is cancer a disease of self-seeding?

The high cell density, rapid growth rate and large population size of cancer are conventionally attributed to a pathologically high ratio of cell production to cell death. Yet these features might also or instead result from inappropriate cell movement, already understood to underlie invasion and metastasis. This integrating concept could induce a broadening of our existing anticancer pharmacopoeia, which, with mitosis as its predominant target, is now seldom curative.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Figure 1: The self-seeding concept of cancer growth and metastasis.
Figure 2: Gompertzian growth curves.

References

  1. 1

    Hanahan, D. & Weinberg, R.A. Cell 100, 57–70 (2000).

    CAS  Article  Google Scholar 

  2. 2

    Rizki, A. & Bissell, M.J. Cancer Cell 6, 1–2 (2004).

    CAS  Article  Google Scholar 

  3. 3

    Mott, J.D. & Werb, Z. Curr. Opin. Cell Biol. 16, 558–564 (2004).

    CAS  Article  Google Scholar 

  4. 4

    Lynch, C.C. & Matrisian, L.M. Differentiation 70, 561–573 (2002).

    CAS  Article  Google Scholar 

  5. 5

    Joyce, J.A. Cancer Cell 7, 513–520 (2005).

    CAS  Article  Google Scholar 

  6. 6

    Massague, J. Nature 432, 298–306 (2004).

    CAS  Article  Google Scholar 

  7. 7

    Li, Y., Hively, W.P. & Varmus, H.E. Oncogene 19, 1002–1009 (2000).

    CAS  Article  Google Scholar 

  8. 8

    Garcia, S.B., Park, H.S., Novelli, M. & Wright, N.A. J. Pathol. 187, 61–81 (1999).

    CAS  Article  Google Scholar 

  9. 9

    van de Vijver, M.J. et al. N. Engl. J. Med. 347, 1999–2009 (2002).

    CAS  Article  Google Scholar 

  10. 10

    Chang, H.Y. et al. Proc. Natl. Acad. Sci. USA 102, 3738–3743 (2005).

    CAS  Article  Google Scholar 

  11. 11

    Troester, M.A. et al. Cancer Res. 64, 4218–4226 (2004).

    CAS  Article  Google Scholar 

  12. 12

    Foekens, J.A. et al. J. Clin. Oncol. 24, 1665–1671 (2006).

    CAS  Article  Google Scholar 

  13. 13

    Al-Hajj, M. & Clarke, M.F. Oncogene 23, 7274–7282 (2004).

    CAS  Article  Google Scholar 

  14. 14

    Polyak, K. & Hahn, W.C. Nat. Med. 12, 296–300 (2006).

    CAS  Article  Google Scholar 

  15. 15

    Folkman, J. & Kalluri, R. Cancer Medicine. 6th ed. 161–194 (BC Decker, Hamilton, Ontario, 2003).

    Google Scholar 

  16. 16

    Norton, L. Prog. Clin. Biol. Res. 354A, 109–132 (1990).

    CAS  PubMed  Google Scholar 

  17. 17

    Schneider, B.S., Hastings, H.M. & Maytal, G. Proc. Biol. Sci. 263, 129–131 (1996).

    CAS  Article  Google Scholar 

  18. 18

    Norton, L. Oncologist. 6 Suppl 3, 30–35 (2001).

    CAS  Article  Google Scholar 

  19. 19

    Hutchinson, J.N. & Muller, W.J. Oncogene 19, 6130–6137 (2000).

    CAS  Article  Google Scholar 

  20. 20

    Dang, C., Gilewski, T.A., Surbone, A. & Norton, L. Cytokinetics. in Cancer Medicine 6th edn 645–668 (BC Decker, Hamilton, Ontario, 2003).

    Google Scholar 

  21. 21

    Kang, Y. et al. Cancer Cell 3, 537–549 (2003).

    CAS  Article  Google Scholar 

  22. 22

    Minn, A.J. et al. Nature 436, 518–524 (2005).

    CAS  Article  Google Scholar 

  23. 23

    Kabbinavar, F.F. et al. J. Clin. Oncol. 23, 3706–3712 (2005).

    CAS  Article  Google Scholar 

  24. 24

    Eastern Cooperative Oncology Group. Clin. Lung Cancer 6, 276–278 (2005).

  25. 25

    Miller, K.D. et al. J. Clin. Oncol. 23, 792–799 (2005).

    CAS  Article  Google Scholar 

Download references

Acknowledgements

The authors express their appreciation to A.B. Olshen for his review of mathematical details, to T.J. Riley for drawing the figures, and to C. Pearce for editing the manuscript. We also acknowledge with gratitude discussions with our principal P01-CA94060-04 colleagues—R. Benezra, M. Jasin, S. Larson, M. Moynahan, N. Rosen and H. Varmus—and with J. Bromberg, G. Gupta, C. Hudis, R. Kurtz, A. Minn, D. Spriggs and C. Van Poznak.

Author information

Affiliations

Authors

Corresponding author

Correspondence to Larry Norton.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Norton, L., Massagué, J. Is cancer a disease of self-seeding?. Nat Med 12, 875–878 (2006). https://doi.org/10.1038/nm0806-875

Download citation

Further reading

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing