References
Folkman J: Angiogenesis in cancer. vascular. rheumatoid. and other discase. Nat Med 1: 27-31, 1995
Marmé D: Tumor angiogenesis: The pivotal role of vascular endothelial growth factor (VEGF). World J Urol 14: 166-174, 1996
Ferrara N, Davis-Smyth T: The biology of vascular endothelial growth factor. Endocr Rev 18: 4-25, 1997
Finkenzeller G, Marmé D, Weich HA, Hug H: Platelet de rived growth factor-induced transcription of the vascular endothelial growth factor gene is mediated by protein kinase C. Cancer Res 52: 4821-4823, 1992
Brogi F, Wu T, Namiki A, Isner JM: Indirect angiogenic cytokines upregulate VEGF and bFGF gene expression in vascular smooth musele cells, whereas hypoxia upregulates VEGF expression only. Circulation 90: 649-652, 1994
Detmar M, Brown LF, Claffey KP, Yeo KT, Kocher O, Jackman RW, Berse B, Dvorak HF: Overexpression of vascular permeability factor/vascular endothelial growth factor and its receptors in psoriasis. J Exp Med 180: 1141-1146, 1994
Pertovaara L, Kaipainen A, Mustonen T, Orpana A, Ferrara N, Saksela O, Alitalo K: Vascular endothelial growth factor is induced in response to transforming growth factor-beta in fibroblastic and epithelial cells. J Biol Chem 269: 6271-6274, 1994
Frank S, Hubner G, Breier G, Longaker MT, Greenhalgh DG, Werner S: Regulation of vascular endothelial growth factor expression in cultured keratinocytes. Implications for normal and impaired wound healing. J Biol Chem 270: 12607-12613, 1995
Li J, Perrella MA, Tsai JC, Yet SF, Hsich CM, Yoshizumi M, Patterson C, Endege WO, Zhou F, Lee ME: Induction of vascular endothelial growth factor gene expression by interleukin-1 beta in ral aortic smooth muscle cells. J Biol Chem 270: 308-312, 1995
Cohen T, Nahari D, Cerem LW, Neufeld G, Levi BZ: Interlcukin 6 induces the expression of vascular endothelial growth factor. J Biol Chem 271: 736-741, 1996
Warren RS, Yuan H, Matli MR, Ferrara N, Donner DB: Induction of vascular endothelial growth factor by insulin-like growth factor 1 in colorectal carcinoma. J Biol Chem 271: 29483-29488, 1996
Tischer E, Mitchell R, Hartman T, Silva M, Gospodarowicz D, Fiddes JC, Abraham JA: The human gene for vascular endothelial growth factor. Multiple protein forms are encoded through alternative exon splicing. J Biol Chem 266: 11947-11954, 1991
Gruget S, Finkenzeller G, Weindel K, Barleon B, Marme D: Both v-Ha-Ras and v-Raf stimulate expression of the vascular endothelial growth factor in NIH 3T3 cells. J Biol Chem 270: 25915-25919, 1995
Rak J, Mitsuhashi Y, Bayko L, Filmus J, Shirasawa S, Sasazuki T, Kerbel RS: Mutant ras oncogenes upregulate VEGF/VPF expression: implications for induction and inhibition of tumor angiogenesis. Cancer Res 55: 4575-4580, 1995
Mukhopadhyay D, Tsiokas L, Sukhatme VP: Wild-type p53 and v-Sre exert opposing influences on human vascular endothelial growth factor gene expression. Cancer Res 55: 6161-6165, 1995
Kieser A, Weich HA, Brandner G, Marmé D, Kölch W: Mutant p53 potentiates protein kinase C induction of vascular endothelial growth factor expression. Oncogene 9: 963-969, 1994
Siemeister G, Weindel K, Mohrs K, Barlcon B, Martiny-Baron G, Marmé D: Reversion of deregulated expression of vascular endothelial growth factor in human renal carcinoma cells by von Hippel-Landau tumor suppressor protein. Cancer Res 56: 2299-2301, 1996
Shweiki D, Itin A, Soffer D, Keshet E: Vascular endothelial growth factor induced by hypoxia may mediate hypoxia-initiated angiogenesis. Nature 359: 843-845, 1992
Plate KH, Breier G, Weich HA, Risau W: Vascular endothelial growth factor is a potential tumour angiogenesis factor in human gliomas in vivo. Nature 359: 845-848, 1992
Ryuto M, Ono M, Izumi H, Yoshida S, Weich HA, Kohno K, Kuwano M: Induction of vascular endothelial growth factor by tumor neerosis factor α in human glioma cells: possible roles of Sp-1. J Biol Chem 271: 28220-28228, 1996
Gille J, Swerlick RA, Caughman SW: Transforming growth factor-α-induced transcriptional activation of the vascular permeability factor (VPF/VEGF) gene requires AP-2-dependent DNA binding and transactivation. EMBO J 16: 750-759, 1997
Finkenzeller G, Sparacio A, Technau A, Marmé D, Siemeister G: Sp1 recognition sites in the proximal promoter of the human vascular endothelial growth factor gene are essential for platelet-derived growth factor-induced gene expression. Oncogene 15: 669-676, 1997
Mukhopadhyay D, Knebelmann B, Cohen HT, Ananth S, Sukhatme VP: The von Hippel-Lindau tumor suppressor gene product interacts with Sp1 to repress vascular endothelial growth factor promoter activity. Mol Cell Biol 17: 5629-5639, 1997
Duan DR, Pause A, Burgess WH, Aso T, Chen DYT, Garrett KP, Conaway RC, Conaway JW, Linchan WM, Klausner RD: Inhibition of transcription elongation by the VHL tumor suppresor protein. Science 269: 1402-1406, 1995
Aso T, Lane WS, Conaway JW, Conaway RC: Elongin (SIH): A multisubunit regulator of clongation by RNA polymerase H. Science 269: 1439-1443, 1995
Kibel A, Iliopoulos O, DeCaprio JA, Kaelin WG Jr: Binding of the von Hippel-Lindau tumor suppressor protein to clogin B and C. Science 269: 1444-1446, 1995
Iliopoulos O, Levy AP, Jiang C, Kaclin WG Jr, Goldberg MA: Negative regulation of hypoxia-inducible genes by the von Hippel-Lindau protein. Proc Natl Acad Sci USA 93: 10595-10599, 1996
Ikeda E, Achen MG, Breier G, Risau W: Hypoxia-induced transcriptional activation and increased mRNA stability of vascular endothelial growth factor in C6 glioma cells. J Biol Chem 270: 19761-19766, 1995
Damert A, Machein M, Breier G, Fujita MO, Hanahan D, Risau W, Plate KH: Up-regulation of vascular endothelial growth tactor expression in a rat glioma is conferred by two distinct hypoxia-driven mechanisms. Cancer Res 57: 3860-3864, 1997
Levy AP, Levy NS, Goldberg MA: Post-transcriptonal regulation of vascular endothelial growth factor by hypoxia. J Biol Chem 271: 2746-2753, 1996
Levy AP, Levy NS, Goldberg MA: Hypoxia-inducible protein binding to vascular endothelial growth factor mRNA and its modulation by the von Hippel-Lindau protein. J Biol Chem 271: 25492-25497, 1996
Forsythe JA, Jiang BH, Iyer NV, Agani F, Leung SW, Koos RD, Semenza GL: Activation of vascular endothelial growth factor gene transcription by hypoxia-inducible factor 1. Mol Cell Biol 16: 4604-4613, 1996
Damert A, Ikeda E, Risau W: Activator-protein-1 binding potentiates the hypoxia-inducible factor-1-mediated hypoxia-induced transcriptional activation of vascular endothelial growth factor expression in C6 glioma cells. Biochem J 327: 419-423, 1997
Mazure NM, Chen EY, Yeh P, Laderoute KR, Giaccia AJ: Oncogenic transformation and hypoxia synergistically act to modulate vascular endothelial growth factor expression. Cancer Res 56: 3436-3440, 1996
Mazure NM, Chen EY, Laderoute KR, Giaccia AJ: Induction of vascular endothelial growth factor by hypoxia is modulated by a phosphatidylinositol 3-kinase/Akt signaling pathway in Ha-ras-transformed cells through a hypoxia inducible element. Blood 90: 3322-3331, 1997
Arbiser JL, Moses MA, Fernandez CA, Ghiso N, Cao Y, Klauber N, Frank D, Brownlee M, Flynn E, Parangi S, Byers HR, Folkman J: Oncogenic H ras stimulates tumor angiogenesis by two distinet pathways. Proc Natl Acad Sci USA 94: 861-866, 1997
Mukhopadhyay D, Tsiokas L, Zhou XM, Foster D, Brugge JS, Sukhatme VP: Hypoxic induction of human vascular endothelial growth factor expression through c-Src activation. Nature 375: 577-581, 1995
Gleadle JM, Ratcliffe PJ: Induction of hypoxia-inducible factor-1, crythropoietin, vascular endothelial growth factor, and glucose transporter-1 by hypoxia: evidence against a regulatory role for src kinase. Blood 89: 503-509, 1997
Kevil CG, De Benedetti A, Payne DK, Coe LL, Laroux FS, Alexander JS: Translational regulation of vascular permeability factor by cukaryotic initiation factor 4E: implications for tumor angiogenesis. Int J Cancer 65: 785-790, 1996
Kerekatte V, Smilcy K, Hu B, Smith A, Gelder F, De Benedetti A: The proto-oncogene/translation factor cIF4E: a survey of its expression in breast carcinomas. Int J Cancer 64: 27-31, 1995
Miyagi Y, Sugiyama A, Asai A, Okazaki T, Kuchino Y, Kerr SJ: Elevated levels of cukaryotic translation initiation factor eIF-4E mRNA in a broad spectrum of transformed cell lines. Cancer L 91: 247-252, 1995
Olander JV, Connolly DT, DeLarco JE: Specific binding of vascular permeability factor to endothelial cells. Biochem Biophys Res Commun 175: 68-76, 1991
Quinn TP, Peters KG, De Vries C, Ferrara N: Fetal liver kinase 1 is a receptor for vascular endothelial growth factor and is selectively expressed in vascular endothelium. Proc Natl Acad Sci USA 90: 7533-7537, 1993
Peters KG, De Vries C, Williams LT: Vascular endothelial growth factor expression during embryogenesis and tissue repair suggests a role in endothelial differentiation and blood vessel growth. Proc Natl Acad Sci USA 90: 8915-8919, 1993
Millauer B, Wizigmann-Voos S, Schnürch H, Martinez R, Miller NPH, Risau W, Ullrich A: High affinity VEGT binding and developmental expression suggest Flk-1 as a major regulator of vasculogenesis and angiogenesis. Cell 72: 835-846, 1993
Klagsbrun M, D'Amore PA: Regulators of angiogenesis. Ann Rev Physiol 53: 217-239, 1991
Frater-Schroder M, Risau W, Hallmann R, Gautsch P: Tumor necrosis factor type α, a potent inhibitor of endothelial cell growth in vitro, is angiogenic in vivo. Proc Natl Acad Sci USA 84: 5277-5281, 1987
Leibovich S, Polverini P, Shepard H, Wisoman D, Shively V, Nuscir N: Macrophage-induced angiogenesis is mediated by tumour necrosis factor-α. Nature 329: 630-632
Patterson C, Perrella MA, Endege WO, Yoshizumi M, Lee M-E, Haber E: Downregulation of vascular endothelial growth factor by tumor necrosis factor-α in cultured human vascular endothelial cells. J Clin Invest 98: 490-496, 1996
Mandnota SJ, Menoud P-A, Pepper MS: Transforming growth factor β1 down-regulates vascular endothelial growth factor receptor 2/flk-1 expression in vascular endothelial cells. J Biol Chem 271: 11500-11505, 1996
Kremer C, Breier G, Risau W, Plate KH: Up-regulation of flk-1/vascular endothelial growth factor receptor 2 by its ligand in a cerebral slice culture system. Cancer Res 57: 3852-3859, 1997
Barleon B, Siemeister G, Martiny-Baron G, Weindel K, Herzog C, Marmé D: Vascular endothelial growth factor up-regulates its receptor fms-like tytosine kinase 1 (FLT-1) and a soluble variant of FLT-1 in human vascular endothelial cells. Cancer Res 57: 5421-5425, 1997
Tuder RM, Flook BE, Voelkel NF: Increased gene expression for VEGF and the VEGF receptors KDR/Flk and Flt in lungs exposed to acute or to chronic hypoxia. J Clin Invest 95: 1798-1807, 1995
Detmar M, Brown LF, Berse B, Jackman RW, Elicker BM, Dvorak HF, Claffey KP: Hypoxia regulates the expression of vascular permeability factor/vascular endothelial growth factor (VPF/VEGF) and its receptor in human skin. J Invest Dermatol 108: 263-268, 1997
Thieme H, Aiello LP, Takagi H, Ferrara N, King GL: Comparative analysis of vascular endothelial growth factor receptors on retinal and aortic vascular endothelial cells. Diabetes 44: 98-103, 1995
Brogi E, Schatteman G, Wu T, Kim EA, Varticovski L, Keyt B, Isner JM: Hypoxia-induced paracrine regulation of vascular endothelial growth factor receptor expression. J Clin Invest 97: 469-476, 1996
Morishita K, Johnson DE, Williams LT: A novel promoter for vascular endothelial growth factor (flt-1) that confers endothelial specific gene expression. J Biol Chem 270: 27948-27953, 1995
Patterson C, Perrella MA, Hsich C-M, Yoshizumi M, Lee M-E, Haber E: Cloning and functional analysis of the promoter for KDR/flk-1, a receptor for vascular endothelial growth factor. J Biol Chem 270: 23111-23118, 1995
Rönicke V, Risau W, Breier G: Characterization of the endothelium-specific murine vascular endothelial growth factor receptor-2 (Flk-1) promoter. Circ Res 79: 277-285, 1996
Gerber H-P, Condorclli B, Park J, Ferrara N: Differential transcriptional regulation of the two vascular endothelial growth factor receptor genes. J Biol Chem 272: 23659-23667, 1997
Millauer B, Shawver KL, Plate KH, Risau W, Ullrich A: Glioblastoma growth inhibited in vivo by a dominant-negative Flk-1 mutant. Nature 367: 576-579, 1994
Kim KJ, Li B, Winer J, Armanini M, Gillett N, Phillips HS, Fenara N: Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumour growth in vivo. Nature 362: 841-844, 1993
Borgström P, Hillan KJ, Sriramarao P, Ferrara N: Complete inhibition of angiogenesis and growth of microtumors by anti-vascular endothelial growth factor neutralizing antibodies. Novel concepts of angiostatic therapy from intravital videomicroscopy. Cancer Res 56: 4032-4039, 1996
Warren RA, Yuan H, Matli MR, Gillett NA, Ferrara N: Regulation by vascular endothelial growth factor of human colon cancer tumorigeneses in a mouse model of experimental liver metastasis. J Clin Invest 95: 1789-1797, 1995
Saleh M, Stacker SA, Wilks AF: Inhibition of growth of C6 glioma cells in vivo by expression of antisense vascular endothelial growth factor sequence. Cancer Res 56: 393-401, 1996
Petit AMV, Rak J, Hung M-C, Rockwell P, Goldstein N, Fendly B, Kerbel RS: Neutralizing antibodies against epidermal growth factor and ErbB-2/neu receptor tyrosine kinases down-regulate vascular endothelial growth factor production by tumor cells in vitro and in vivo: Angiogenic implications for signal transduction therapy of solid tumors. Am J Pathol 151: 1523-1530, 1997
Skobe M, Rockwell P, Goldstein N, Vosseler S, Fusenig NE: Halting angiogenesis suppresses carcinoma cell invasion. Nature Med 3: 1222-1227, 1997
Relf M, LeJeune S, Scott PAE, Fox S, Smith K, Leek R, Moghaddam A, Whitehouse R, Bicknell R, Harris AL: Expression of the angiogenic factors vascular endothelial growth factor, acidic and basic fibroblast growth factor, tumor growth factor β-1, platelet-derived endothelial cell growth factor, placenta growth factor, and pleiotrophin in human primary breast cancer and its relation to angiogenesis. Cancer Res 57: 963-969, 1997
Ramakrishnan S, Olson TA, Bautch VL, Mohanraj D: Vascular endothelial growth factor-toxin conjugate specifically inhibits KDR/flk-1-positive endothelial cell proliferation in vitro and angiogenesis in vivo. Cancer Res 56: 1324-1330, 1996
Strawn LM, McMahon G, App H, Schreck R, Kuchler WR, Longhi MP, Hui TH, Tang C, Levitzki A, Gazit A, Chen I, Keri G, Orfi L, Risau W, Flamme I, Ullrich A, Hirth KP, Shawver LK: Flk-1 as a target for tumor growth inhibition. Cancer Res 56: 3540-3545, 1996
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Siemeister, G., Martiny-Baron, G. & Marmé, D. The pivotal role of VEGF in tumor angiogenesis: Molecular facts and therapeutic opportunities. Cancer Metastasis Rev 17, 241–248 (1998). https://doi.org/10.1023/A:1006027124696
Issue Date:
DOI: https://doi.org/10.1023/A:1006027124696