Angiogenic and cell survival functions of Vascular Endothelial Growth Factor (VEGF)

被引:563
作者
Byrne, AM [1 ]
Bouchier-Hayes, DJ [1 ]
Harmey, JH [1 ]
机构
[1] Royal Coll Surgeons Ireland, Dept Surg, Educ & Res Ctr, Beaumont Hosp, Dublin 9, Ireland
关键词
VEGF; angiogenesis; cell survival; tumour angiogenesis; chemotherapy; hypoxia;
D O I
10.1111/j.1582-4934.2005.tb00379.x
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Vascular endothelial growth factor (VEGF) was originally identified as an endothelial cell specific growth factor stimulating angiogenesis and vascular permeability. Some family members, VEGF C and D, are specifically involved in lymphangiogenesis. It now appears dial VEGF also has autocrine functions acting as a survival factor for tumour cells protecting them from stresses such as hypoxia, chemotherapy and radiotherapy. The mechanisms of action of VEGF are still being investigated with emerging insights into overlapping pathways and cross-talk between other receptors such as the neuropilins which were not previously associated with angiogenesis. VEGF plays an important role in embryonic development and angiogenesis during wound healing and menstrual cycle in the healthy adult. VEGF is also important in a number of both malignant and non-malignant pathologies. As it plays a limited role in normal human physiology, VEGF is an attractive therapeutic target in diseases where VEGF plays a key role. It was originally thought that in pathological conditions such as cancer, VEGF functioned solely as an angiogenic factor, stimulating new vessel formation and increasing vascular permeability. It has since emerged it plays a multifunctional role where it can also have autocrine pro-survival effects and contribute to tumour cell chemoresistance. In this review we discuss the established role of VEGF in angiogenesis and the underlying mechanisms. We discuss its role as a survival factor and mechanisms whereby angiogenesis inhibition improves efficacy of chemotherapy regimes. Finally, we discuss the therapeutic implications of targeting angiogenesis and VEGF receptors, particularly in cancer therapy.
引用
收藏
页码:777 / 794
页数:18
相关论文
共 138 条
  • [91] Neuropilin-1 in human colon cancer - Expression, regulation, and role in induction of angiogenesis
    Parikh, AA
    Fan, F
    Liu, WB
    Ahmad, SA
    Stoeltzing, O
    Reinmuth, N
    Bielenberg, D
    Bucana, CD
    Klagsbrun, M
    Ellis, LM
    [J]. AMERICAN JOURNAL OF PATHOLOGY, 2004, 164 (06) : 2139 - 2151
  • [92] Expression and regulation of the novel vascular endothelial growth factor receptor neuropilin-1 by epidermal growth factor in human pancreatic carcinoma
    Parikh, AA
    Liu, WB
    Fan, F
    Stoeltzing, O
    Reinmuth, N
    Bruns, CJ
    Bucana, CD
    Evans, DB
    Ellis, LM
    [J]. CANCER, 2003, 98 (04) : 720 - 729
  • [93] PARK JE, 1993, MOL BIOL CELL, V4, P1317, DOI 10.1091/mbc.4.12.1317
  • [94] PARK JE, 1994, J BIOL CHEM, V269, P25646
  • [95] Extracellular signal-regulated protein kinase Jun kinase cross-talk underlies vascular endothelial cell growth factor-induced endothelial cell proliferation
    Pedram, A
    Razandi, M
    Levin, ER
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (41) : 26722 - 26728
  • [96] Vascular endothelial growth factor (VEGF) upregulates BCL-2 and inhibits apoptosis in human and murine mammary adenocarcinoma cells
    Pidgeon, GP
    Barr, MP
    Harmey, JH
    Foley, DA
    Bouchier-Hayes, DJ
    [J]. BRITISH JOURNAL OF CANCER, 2001, 85 (02) : 273 - 278
  • [97] Price DJ, 2001, CELL GROWTH DIFFER, V12, P129
  • [98] VEGF-induced activation of phosphoinositide 3-kinase is dependent on focal adhesion kinase
    Qi, JH
    Claesson-Welsh, L
    [J]. EXPERIMENTAL CELL RESEARCH, 2001, 263 (01) : 173 - 182
  • [99] Reynolds LP, 1998, J ANIM SCI, V76, P1671
  • [100] Riedel F, 2004, ANTICANCER RES, V24, P2179