Glioblastoma growth inhibited in vivo by a dominant-negative Flk-1 mutant (original) (raw)

Nature volume 367, pages 576–579 (1994)Cite this article

Abstract

ANGIOGENESIS, the sprouting of capillaries from pre-existing blood vessels, is a fundamental process in the formation of the vascular system during embryonic development. In adulthood, angiogenesis takes place during corpus luteum formation and in pathological conditions such as wound healing, diabetic retinopathy, and tumorigenesis. Vascularization is essential for solid tumour growth and is thought to be regulated by tumour cell-produced factors, which have a chemotactic and mitogenic effect on endothelial cells1–4. Vascular endothelial growth factor (VEGF), a homodimeric glycoprotein of relative molecular mass 45,000, is the only mitogen, however, that specifically acts on endothelial cells, and it may be a major regulator of tumour angiogenesis _in vivo_5,6. Its expression has been shown to be upregulated by hypoxia, and its cell-surface receptor, FIk-1, is exclusively expressed in endothelial cells7,8. Here we investigate the biological relevance of the VEGF/Flk-1 receptor/ligand system for angiogenesis using a retrovirus encoding a dominant-negative mutant of the Flk-1/VEGF receptor to infect endothelial target cells in vivo, and find that tumour growth is prevented in nude mice. Our results emphasize the central role of the FIk-1/VEGF system in angiogenesis in general and in the development of solid tumours in particular.

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Author notes

  1. Axel Ullrich: To whom all correspondence should be addressed.

Authors and Affiliations

  1. Department of Molecular Biology, Max-Planck-lnstitut fur Biochemie, Am Klopferspitz ISA, 82152, Martinsried, Germany
    Birgit Millauer & Axel Ullrich
  2. SUGEN Inc., 515 Galveston Drive, Redwood City, California, 94063, USA
    Laura K. Shawver
  3. Department of Molecular Cell Biology, Max-Planck-lnstitut fur physiologische und klinische Forschung, W. G. Kerckhoff Institut, 61231, Bad Nauheim, Germany
    Karl H. Plate & Werner Risaui

Authors

  1. Birgit Millauer
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  2. Laura K. Shawver
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  3. Karl H. Plate
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  4. Werner Risaui
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  5. Axel Ullrich
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Millauer, B., Shawver, L., Plate, K. et al. Glioblastoma growth inhibited in vivo by a dominant-negative Flk-1 mutant.Nature 367, 576–579 (1994). https://doi.org/10.1038/367576a0

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