Skip to main content

Thank you for visiting nature.com. 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.

  • Brief Communication
  • Published:

Growth factors

Formation of endothelial cell networks

Abstract

The growth factor VEGF (vascular endothelial growth factor) promotes the formation of blood vessels in a process known as angiogenesis by inducing the proliferation and migration of endothelial cells1. We show here that VEGF has another proangiogenic function — it can stimulate the elongation, network formation and branching of non-proliferating endothelial cells in culture that are deprived of oxygen and nutrients. As endothelial cells in tumours are exposed to chronic or intermittent hypoxic conditions2,3, we propose that autocrine endothelial VEGF contributes to the formation of blood vessels in a tumour and promotes its survival.

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

Figure 1: VEGF produced by endothelial cells (ECs) promotes network formation in the hypoxic region of tumour-mimetic sandwich cultures.
Figure 2: Measurement of spatial and temporal gradients of pO2 and VEGF, and segment and branch lengths across the width of HUVEC sandwich cultures.

Similar content being viewed by others

References

  1. Carmeliet, P. Nature Med. 6, 389–395 (2000).

    Article  CAS  Google Scholar 

  2. Helmlinger, G., Yuan, F., Dellian, M. & Jain, R. K. Nature Med. 3, 177–182 (1997).

    Article  CAS  Google Scholar 

  3. Kimura, H. et al. Cancer Res. 56, 5522– 5528 (1996).

    CAS  PubMed  Google Scholar 

  4. Hlatky, L. & Alpen, E. L. Cell Tissue Kinet. 18, 597–611 (1985).

    CAS  PubMed  Google Scholar 

  5. Hlatky, L., Hahnfeldt, P., Tsionou, C. & Coleman, C. N. Br. J. Cancer. 74, S151–S156 (1996).

    CAS  Google Scholar 

  6. Hlatky, L. et al. Cancer Res. 54, 6083– 6086 (1994).

    CAS  PubMed  Google Scholar 

  7. Ferrara, N. & Davis-Smyth, T. Endocr. Rev. 18, 4–25 (1997).

    Article  CAS  Google Scholar 

  8. Nomura, M. et al. J. Biol. Chem. 270, 28316– 28324 (1995).

    Article  CAS  Google Scholar 

  9. Sholley, M. M. et al. Lab Invest. 51, 624– 634 (1984).

    CAS  PubMed  Google Scholar 

  10. Patan, S., Munn, L. & Jain, R. K. Microvasc. Res. 51, 260– 272 (1996).

    Article  CAS  Google Scholar 

  11. Namiki, A. et al. J. Biol. Chem. 270, 31189– 31195 (1995).

    Article  CAS  Google Scholar 

  12. Liu, Y. et al. J. Biol. Chem. 273, 15257– 15262 (1998).

    Article  CAS  Google Scholar 

  13. Torres Filho, I. P. & Intaglietta, M. Am. J. Physiol. 265, H1434–H1438 ( 1993).

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Cite this article

Helmlinger, G., Endo, M., Ferrara, N. et al. Formation of endothelial cell networks. Nature 405, 139–141 (2000). https://doi.org/10.1038/35012132

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/35012132

Comments

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.

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