Abstract
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.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
196,21 € per year
only 3,85 € per issue
Buy this article
- Purchase on SpringerLink
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Weidner, N., Semple, J. P., Welch, W. R. & Folkman, J. New Engl. J. Med. 324, 1–8 (1991).
Folkman, J. J. natn. Cancer Inst. 82, 4–6 (1990).
Folkman, J. & Klagsbrun, M. Science 235, 442–447 (1987).
Risau, W. Progress in Growth Factor Research 2, 71–79 (1990).
Russel, D. C. & Rubinstein, L. J. Pathology of Tumours of the Nervous System 5th edn (Arnold, London, 1989).
Germano, I. M. et al. J. Neurosurg. 70, 701–706 (1989).
Folkman, J. & Shing, Y. J. biol. Chem. 267, 10931–10934 (1992).
Klagsbrun, M. & Folkman, J. Handbook of Experimental Pharmacology Vol. 95/II, 549–586 (Springer. Berlin, 1990).
Bouck, N. Cancer Cells 2, 179–185 (1990).
Folkman, J., Watson, K., Ingber, D. & Hanahan, D. Nature 339, 58–61 (1989).
Liotta, L. A., Steeg, P. S. & Stetler-Stevensohn, W. G. Cell 64, 327–336 (1991).
Plate, K. H., Breier, G., Farrell, C. & Risau, W. Lab. Invest. 67, 529–534 (1992).
Risau, W. et al. Growth Factors (in the press).
Ferrara, N., Houck, K. A., Jakeman, L. B., Winer, J. & Leung, D. W. J. cell. Biochem. 47, 211–218 (1991).
Breier, G., Albrecht, U., Sterrer, S. & Risau, W. Development 114, 521–532 (1992).
Berse, B., Brown, L. F., Van de Water, L., Dvorak, H. F. & Senger, D. R. Molec. Biol. Cell 3, 211–220 (1992).
Conn, G. et al. Proc. natn. Acad. Sci. U.S.A. 87, 1323–1327 (1990).
Weindel, K., Marmé, D. & Weich, H. Biochem. biophys. Res. Commun. 183, 1167–1174 (1992).
Leung, D. W., Cachianes, G., Kuang, W.-J., Goeddel, D. V. & Ferrara, N. Science 246, 1306–1309 (1989).
Jakeman, L. B., Winer, J., Bennett, G. L., Altar, C. A. & Ferrara, N. J. clin. Invest. 89, 244–253 (1992).
Burger, P. & Green, S. Cancer 59, 1617–1625 (1987).
Ingber, D. et al. Nature 348, 555–557 (1990).
Folkman, J. in Biological Therapy of Cancer (eds Devita, V. T., Hellman, S. & Rosenberg, S. A.) 743–753 (Lippincott, Philadelphia, 1991).
Brem, S. B. et al. Am. J. Path. 137, 1121–1142 (1990).
De Vries, C. et al. Science 255, 989–991 (1992).
Dvorak, H. F. et al. J. exp. Med. 174, 1275–1278 (1991).
Jain, R. K. Cancer Res. 48, 2641–2658 (1988).
Sidransky, D. et al. Nature 355, 846–847 (1992).
Kern, S. E. et al. Science 256, 827–830 (1992).
Scherer, H.-J. Virchows Arch. 294, 823–861 (1935).
Shibuya, M. et al. Oncogene 5, 519–524 (1990).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
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). https://doi.org/10.1038/359845a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/359845a0
