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Vascular endothelial growth factor is a potential tumour angiogenesis factor in human gliomas in vivo


CLINICAL and experimental studies suggest that angiogenesis is a prerequisite for solid tumour growth1,2. Several growth factors with mitogenic or chemotactic activity for endothelial cells in vitro have been described, but it is not known whether these mediate tumour vascularization in vivo3,4. Glioblastoma, the most common and most malignant brain tumour in humans, is distinguished from astrocytoma by the presence of necroses and vascular prolifer-ations5'6. Here we show that expression of an endothelial cell-specific mitogen, vascular endothelial growth factor (VEGF), is induced in astrocytoma cells but is dramatically upregulated in two apparently different subsets of glioblastoma cells. The high-affinity tyrosine kinase receptor for VEGF, flt, although not expressed in normal brain endothelium, is upregulated in tumour endothelial cells in vivo. These observations strongly support the concept that tumour angiogenesis is regulated by paracrine mechanisms and identify VEGF as a potential tumour angiogenesis factor in vivo.

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  1. 1

    Weidner, N., Semple, J. P., Welch, W. R. & Folkman, J. New Engl. J. Med. 324, 1–8 (1991).

    CAS  Article  Google Scholar 

  2. 2

    Folkman, J. J. natn. Cancer Inst. 82, 4–6 (1990).

    CAS  Article  Google Scholar 

  3. 3

    Folkman, J. & Klagsbrun, M. Science 235, 442–447 (1987).

    ADS  CAS  Article  Google Scholar 

  4. 4

    Risau, W. Progress in Growth Factor Research 2, 71–79 (1990).

    CAS  Article  Google Scholar 

  5. 5

    Russel, D. C. & Rubinstein, L. J. Pathology of Tumours of the Nervous System 5th edn (Arnold, London, 1989).

    Google Scholar 

  6. 6

    Germano, I. M. et al. J. Neurosurg. 70, 701–706 (1989).

    CAS  Article  Google Scholar 

  7. 7

    Folkman, J. & Shing, Y. J. biol. Chem. 267, 10931–10934 (1992).

    CAS  Google Scholar 

  8. 8

    Klagsbrun, M. & Folkman, J. Handbook of Experimental Pharmacology Vol. 95/II, 549–586 (Springer. Berlin, 1990).

    Google Scholar 

  9. 9

    Bouck, N. Cancer Cells 2, 179–185 (1990).

    CAS  PubMed  Google Scholar 

  10. 10

    Folkman, J., Watson, K., Ingber, D. & Hanahan, D. Nature 339, 58–61 (1989).

    ADS  CAS  Article  Google Scholar 

  11. 11

    Liotta, L. A., Steeg, P. S. & Stetler-Stevensohn, W. G. Cell 64, 327–336 (1991).

    CAS  Article  Google Scholar 

  12. 12

    Plate, K. H., Breier, G., Farrell, C. & Risau, W. Lab. Invest. 67, 529–534 (1992).

    CAS  PubMed  Google Scholar 

  13. 13

    Risau, W. et al. Growth Factors (in the press).

  14. 14

    Ferrara, N., Houck, K. A., Jakeman, L. B., Winer, J. & Leung, D. W. J. cell. Biochem. 47, 211–218 (1991).

    CAS  Article  Google Scholar 

  15. 15

    Breier, G., Albrecht, U., Sterrer, S. & Risau, W. Development 114, 521–532 (1992).

    CAS  Google Scholar 

  16. 16

    Berse, B., Brown, L. F., Van de Water, L., Dvorak, H. F. & Senger, D. R. Molec. Biol. Cell 3, 211–220 (1992).

    CAS  Article  Google Scholar 

  17. 17

    Conn, G. et al. Proc. natn. Acad. Sci. U.S.A. 87, 1323–1327 (1990).

    ADS  CAS  Article  Google Scholar 

  18. 18

    Weindel, K., Marmé, D. & Weich, H. Biochem. biophys. Res. Commun. 183, 1167–1174 (1992).

    CAS  Article  Google Scholar 

  19. 19

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

    ADS  CAS  Article  Google Scholar 

  20. 20

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

    CAS  Article  Google Scholar 

  21. 21

    Burger, P. & Green, S. Cancer 59, 1617–1625 (1987).

    CAS  Article  Google Scholar 

  22. 22

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

    ADS  CAS  Article  Google Scholar 

  23. 23

    Folkman, J. in Biological Therapy of Cancer (eds Devita, V. T., Hellman, S. & Rosenberg, S. A.) 743–753 (Lippincott, Philadelphia, 1991).

    Google Scholar 

  24. 24

    Brem, S. B. et al. Am. J. Path. 137, 1121–1142 (1990).

    CAS  PubMed  Google Scholar 

  25. 25

    De Vries, C. et al. Science 255, 989–991 (1992).

    ADS  CAS  Article  Google Scholar 

  26. 26

    Dvorak, H. F. et al. J. exp. Med. 174, 1275–1278 (1991).

    CAS  Article  Google Scholar 

  27. 27

    Jain, R. K. Cancer Res. 48, 2641–2658 (1988).

    CAS  PubMed  Google Scholar 

  28. 28

    Sidransky, D. et al. Nature 355, 846–847 (1992).

    ADS  CAS  Article  Google Scholar 

  29. 29

    Kern, S. E. et al. Science 256, 827–830 (1992).

    ADS  CAS  Article  Google Scholar 

  30. 30

    Scherer, H.-J. Virchows Arch. 294, 823–861 (1935).

    Article  Google Scholar 

  31. 31

    Shibuya, M. et al. Oncogene 5, 519–524 (1990).

    CAS  PubMed  Google Scholar 

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Plate, K., Breier, G., Weich, H. et al. Vascular endothelial growth factor is a potential tumour angiogenesis factor in human gliomas in vivo. Nature 359, 845–848 (1992).

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