Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumour growth in vivo


THE development of new blood vessels (angiogenesis) is required for many physiological processes including embryogenesis, wound healing and corpus luteum formation1,2. Blood vessel neoformation is also important in the pathogenesis of many disorders1–5, particularly rapid growth and metastasis of solid tumours3–5. There are several potential mediators of tumour angiogenesis, including basic and acidic fibroblast growth factors, tumour necrosis factor-α and transforming factors-α and -β 1,2. But it is unclear whether any of these agents actually mediates angiogenesis and tumour growth in vivo. Vascular endothelial growth factor (VEGF) is an endothelial cell-specific mitogen and an angiogenesis inducer released by a variety of tumour cells and expressed in human tumours in situ. To test whether VEGF may be a tumour angiogenesis factor in vivo, we injected human rhabdomyosar-coma, glioblastoma multiforme or leiomyosarcoma cell lines into nude mice. We report here that treatment with a monoclonal antibody specific for VEGF inhibited the growth of the tumours, but had no effect on the growth rate of the tumour cells In vitro. The density of vessels was decreased in the antibody-treated tumours. These findings demonstrate that inhibition of the action of an angiogenic factor spontaneously produced by tumour cells may suppress tumour growth in vivo.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others


  1. Klagsbrun, M. & D'Amore, P. A. A. Rev. Physiol. 53, 217–239 (1991).

    Article  CAS  Google Scholar 

  2. Folkman, J. & Shing, Y. J. biol. Chem. 267, 10931–11934 (1992).

    CAS  PubMed  Google Scholar 

  3. Folkman, J. J. natn. Cancer Inst. 82, 4–6 (1991).

    Article  Google Scholar 

  4. Ingber, D. et al. Nature 348, 555–557 (1990).

    Article  ADS  CAS  Google Scholar 

  5. Weidner, N., Semple, P., Welch, W. & Folkman, J. N. Engl. J. Med. 324, 1–5 (1991).

    Article  CAS  Google Scholar 

  6. Ferrara, N., Houck, K. A., Jakeman, L. B. & Leung, D. W. Endocr. Rev. 13, 18–32 (1992).

    Article  CAS  Google Scholar 

  7. Ferrara, N. & Henzel, W. J. Biochem. biophys. Res. Commun. 161, 851–858 (1989).

    Article  CAS  Google Scholar 

  8. Ploüet, J., Schilling, J. & Gospodarowicz, D. EMBO J. 8, 3801–3806 (1989).

    Article  Google Scholar 

  9. Conn, G. et al. Proc. natn. Acad. Sci. U.S.A. 87, 2628–2632 (1990).

    Article  ADS  CAS  Google Scholar 

  10. Jakeman, L. B., Winer, J., Bennett, G. L., Altar, C. A. & Ferrara, N. J. clin. Invest. 89, 244–253 (1992).

    Article  CAS  Google Scholar 

  11. Connolly, D. T. et al. J. biol. Chem 264, 20017–20024 (1989).

    CAS  PubMed  Google Scholar 

  12. Keck, P. J. et al. Science 246, 1309–1311 (1989).

    Article  ADS  CAS  Google Scholar 

  13. Leung, D., Cachianes, G., Kuang, W.-J., Goeddel, D. V. & Ferrara, N. Science 246, 1306–1309 (1989).

    Article  ADS  CAS  Google Scholar 

  14. Houck, K. A. et al. Molec. Endocr. 5, 1806–1814 (1991).

    Article  CAS  Google Scholar 

  15. Tisher, E. et al. J. biol. Chem. 266, 11947–11954 (1991).

    Google Scholar 

  16. Houck, K. A., Leung, D. W., Rowland, A. M., Winer, J. & Ferrara, N. J. biol. Chem. 267, 26031–26037 (1992).

    CAS  PubMed  Google Scholar 

  17. Phillips, H. S., Hains, J., Leung, D. W. & Ferrara, N. Endocrinology 127, 965–967 (1990).

    Article  CAS  Google Scholar 

  18. Breier, G., Albrecht, U., Sterrer, S. & Risau, W. Development 114, 521–528 (1992).

    CAS  PubMed  Google Scholar 

  19. Senger, D., Perruzzi, C. A., Feder, J. & Dvorak, H. F. Cancer Res. 46, 5629 (1986).

    CAS  PubMed  Google Scholar 

  20. Rosenthal, R., Megyesi, J. F., Henzel, W. J., Ferrara, N. & Folkman, J. Growth Factors 4, 53–59 (1990).

    Article  CAS  Google Scholar 

  21. Berse, B., Brown, L. F., Van de Water, L., Dvorak, H. F. & Senger, D. R. Molec. biol. Cell 3, 211–218 (1992).

    Article  CAS  Google Scholar 

  22. Shweiki, D., Itin, A., Soffer, D. & Keshet, E. Nature 359, 843–845 (1992).

    Article  ADS  CAS  Google Scholar 

  23. Plate, K. H., Breier, G., Weich, H. A. & Risau, W. Nature 359, 845–847 (1992).

    Article  ADS  CAS  Google Scholar 

  24. Berkman, R. A. et al. J. clin. Invest. 91, 153–159 (1993).

    Article  CAS  Google Scholar 

  25. Ferrara, N. et al. J. clin. Invest. 91, 160–170 (1993).

    Article  CAS  Google Scholar 

  26. Kim, K. J., Li, B., Houck, K., Winer, J. & Ferrara, N. Growth Factors 7, 53–64 (1992).

    Article  CAS  Google Scholar 

  27. Lieberman, T. A. et al. EMBO J. 6, 1627–1632 (1987).

    Article  Google Scholar 

  28. Schweigerer, L. et al. Proc. natn Acad. Sci. U.S.A. 84, 842–846 (1987).

    Article  ADS  CAS  Google Scholar 

  29. Rizzino, A. Meth. Enzym. 146, 341–348 (1987).

    Article  CAS  Google Scholar 

  30. Westphal, M. et al. Expl cell. Biol. 55, 152–161 (1987).

    CAS  Google Scholar 

  31. Berman, P. W. et al. J. Virol. 63, 3489–3498 (1989).

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Ravindranath, N., Little-Ihrig, L., Phillips, H. S., Ferrara, N. & Zeleznick, A. J. Endocrinology 131, 254–260 (1992).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations


Rights and permissions

Reprints and permissions

About this article

Cite this article

Kim, K., Li, B., Winer, J. et al. Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumour growth in vivo. Nature 362, 841–844 (1993).

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI:

This article is cited by


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.


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