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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.

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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.

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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 

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

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