VEGF-A splicing: the key to anti-angiogenic therapeutics?

被引:386
作者
Harper, Steven J. [1 ]
Bates, David O. [1 ]
机构
[1] Univ Bristol, Sch Vet Sci, Bristol Heart Inst, Microvasc Res Labs,Dept Physiol & Pharmacol, Bristol BS2 8EJ, Avon, England
关键词
D O I
10.1038/nrc2505
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The physiology of microvessels limits the growth and development of tumours. Tumours gain nutrients and excrete waste through growth-associated microvessels. New anticancer therapies target this microvasculature by inhibiting vascular endothelial growth factor A (VEGF-A) splice isoforms that promote microvessel growth. However, certain VEGF-A splice isoforms in normal tissues inhibit growth of microvessels. Thus, it is the VEGF-A isoform balance, which is controlled by mRNA splicing, that orchestrates angiogenesis. Here, we highlight the functional differences between the pro-angiogenic and the anti-angiogenic VEGF-A isoform families and the potential to harness the synthetic capacity of cancer cells to produce factors that inhibit, rather than aid, cancer growth.
引用
收藏
页码:880 / 887
页数:8
相关论文
共 78 条
[1]   Exon repression by polypyrimidine tract binding protein [J].
Amir-Ahmady, B ;
Boutz, PL ;
Markovtsov, V ;
Phillips, ML ;
Black, DL .
RNA, 2005, 11 (05) :699-716
[2]   Cellular changes in normal blood capillaries undergoing regression after inhibition of VEGF signaling [J].
Baffert, F ;
Le, T ;
Sennino, B ;
Thurston, G ;
Kuo, CJ ;
Hu-Lowe, D ;
McDonald, DM .
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 2006, 290 (02) :H547-H559
[3]   Small-molecule inhibition of HIV pre-mRNA splicing as a novel antiretroviral therapy to overcome drug resistance [J].
Bakkour, Nadia ;
Lin, Yea-Lih ;
Maire, Sophie ;
Ayadi, Lilia ;
Mahuteau-Betzer, Florence ;
Nguyen, Chi Hung ;
Mettling, Clement ;
Portales, Pierre ;
Grierson, David ;
Chabot, Benoit ;
Jeanteur, Philippe ;
Branlant, Christiane ;
Corbeau, Pierre ;
Tazi, Jamal .
PLOS PATHOGENS, 2007, 3 (10) :1530-1539
[4]  
Bates David O, 2005, Future Oncol, V1, P467, DOI 10.2217/14796694.1.4.467
[5]   Vascular endothelial growth factor increases hydraulic conductivity of isolated perfused microvessels [J].
Bates, DO ;
Curry, FE .
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 1996, 271 (06) :H2520-H2528
[6]  
Bates DO, 2002, CANCER RES, V62, P4123
[7]  
BEVAN HS, 2007, ANGIOGENESIS BASIC S, P1
[8]  
BEVAN HS, NEPHRON PHY IN PRESS
[9]  
BUDGE JR, 2008, MICROCIRCULATION, V17, P18
[10]   An open-and-shut case? Recent insights into the activation of EGF/ErbB receptors [J].
Burgess, AW ;
Cho, HS ;
Eigenbrot, C ;
Ferguson, KM ;
Garrett, TPJ ;
Leahy, DJ ;
Lemmon, MA ;
Sliwkowski, MX ;
Ward, CW ;
Yokoyama, S .
MOLECULAR CELL, 2003, 12 (03) :541-552