FGF and VEGF function in angiogenesis: signalling pathways, biological responses and therapeutic inhibition

被引:794
作者
Cross, MJ [1 ]
Claesson-Welsh, L [1 ]
机构
[1] Uppsala Univ, Rudbeck Lab, Dept Genet & Pathol, S-75185 Uppsala, Sweden
关键词
D O I
10.1016/S0165-6147(00)01676-X
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Angiogenic growth factors such as fibroblast growth factors (FGFs) and vascular endothelial growth factors (VEGFs) are currently targets of intense efforts to inhibit deregulated blood vessel formation in diseases such as cancer. FGFs and VEGFs exert their effects via specific binding to cell surface-expressed receptors equipped with tyrosine kinase activity, Activation of the receptor kinase activity allows coupling to downstream signal transduction pathways that regulate proliferation, migration and differentiation of endothelial cells. Inhibitors of For and VEGF signalling are currently in clinical trials. In this article, the current knowledge of FGF- and VEGF-induced signal transduction that leads to specific biological responses will be summarized. Furthermore, the manner in which this knowledge is being exploited to regulate angiogenesis will be discussed.
引用
收藏
页码:201 / 207
页数:9
相关论文
共 82 条
  • [1] Vascular endothelial growth factor stimulates tyrosine phosphorylation and recruitment to new focal adhesions of focal adhesion kinase and paxillin in endothelial cells
    Abedi, H
    Zachary, I
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (24) : 15442 - 15451
  • [2] Mechanisms of angiogenesis and arteriogenesis
    Carmeliet, P
    [J]. NATURE MEDICINE, 2000, 6 (04) : 389 - 395
  • [3] Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele
    Carmeliet, P
    Ferreira, V
    Breier, G
    Pollefeyt, S
    Kieckens, L
    Gertsenstein, M
    Fahrig, M
    Vandenhoeck, A
    Harpal, K
    Eberhardt, C
    Declercq, C
    Pawling, J
    Moons, L
    Collen, D
    Risau, W
    Nagy, A
    [J]. NATURE, 1996, 380 (6573) : 435 - 439
  • [4] The vascular endothelial growth factor receptor Flt-1 mediates biological activities - Implications for a functional role of placenta growth factor in monocyte activation and chemotaxis
    Clauss, M
    Weich, H
    Breier, G
    Knies, U
    Rockl, W
    Waltenberger, J
    Risau, W
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (30) : 17629 - 17634
  • [5] Skeletal overgrowth and deafness in mice lacking fibroblast growth factor receptor 3
    Colvin, JS
    Bohne, BA
    Harding, GW
    McEwen, DG
    Ornitz, DM
    [J]. NATURE GENETICS, 1996, 12 (04) : 390 - 397
  • [6] Cross MJ, 2000, J CELL SCI, V113, P643
  • [7] Interactions of FLT-1 and KDR with phospholipase C gamma: Identification of the phosphotyrosine binding sites
    Cunningham, SA
    Arrate, MP
    Brock, TA
    Waxham, MN
    [J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1997, 240 (03) : 635 - 639
  • [8] MURINE FGFR-1 IS REQUIRED FOR EARLY POSTIMPLANTATION GROWTH AND AXIAL ORGANIZATION
    DENG, CX
    WYNSHAWBORIS, A
    SHEN, MM
    DAUGHERTY, C
    ORNITZ, DM
    LEDER, P
    [J]. GENES & DEVELOPMENT, 1994, 8 (24) : 3045 - 3057
  • [9] Phosphorylation of the endothelial nitric oxide synthase at Ser-1177 is required for VEGF-induced endothelial cell migration
    Dimmeler, S
    Dernbach, E
    Zeiher, AM
    [J]. FEBS LETTERS, 2000, 477 (03) : 258 - 262
  • [10] Activation of nitric oxide synthase in endothelial cells by Akt-dependent phosphorylation
    Dimmeler, S
    Fleming, I
    Fisslthaler, B
    Hermann, C
    Busse, R
    Zeiher, AM
    [J]. NATURE, 1999, 399 (6736) : 601 - 605