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TY - JOUR AU - Millauer, Birgit AU - Shawver, Laura K. AU - Plate, Karl H. AU - Risaui, Werner AU - Ullrich, Axel PY - 1994 DA - 1994/02/01 TI - Glioblastoma growth inhibited in vivo by a dominant-negative Flk-1 mutant JO - Nature SP - 576 EP - 579 VL - 367 IS - 6463 AB - 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 vivo5,6. 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. SN - 1476-4687 UR - https://doi.org/10.1038/367576a0 DO - 10.1038/367576a0 ID - Millauer1994 ER -