Valproic acid modulates NCAM polysialylation and polysialyltransferase mRNA expression in human tumor cells

被引:28
作者
Beecken, WD [1 ]
Engl, T [1 ]
Ogbomo, H [1 ]
Relja, B [1 ]
Cinatl, J [1 ]
Bereiter-Hahn, E [1 ]
Oppermann, E [1 ]
Jonas, D [1 ]
Blaheta, RA [1 ]
机构
[1] Univ Frankfurt, Zentrum Chirurgie, Klin Urol & Kinderurol Wissenschaft, D-60590 Frankfurt, Germany
关键词
valproic acid; PSA-NCAM; ST8SiaIV; ST8SiaII; tumor dissemination;
D O I
10.1016/j.intimp.2004.12.009
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Polysialic acid (PSA) is a dynamically regulated carbohydrate modification of the neural cell adhesion molecule NCAM, which has been linked to cancer development and dissemination. Two enzymes, the polysialyltransferases ST8SiaIV and ST8SiaII, are known to be involved in the polysialylation of NCAM. The antiepileptic drug valproic acid (VPA) is associated with anti-cancer activity. In this study, VIA blocked the adhesion of several neuroectodermal tumor cell lines to human umbilical vein endothelial cells. Furthermore, VIA induced intracellular PSA accumulation and enhanced expression of PSA-NCAM on the cell surface. Using a semiquantitative RT-PCR strategy, VIA was shown to up-regulate ST8SiaIV mRNA, whereas ST8SiaII mRNA was down-regulated by this compound. Our data indicate that increased expression of ST8SiaIV enables accelerated polysialylation of NCAM, which might be coupled to a loss of adhesive functions of tumor cells. (C) 2004 Elsevier B.V. All rights reserved.
引用
收藏
页码:757 / 769
页数:13
相关论文
共 42 条
[1]   Differential and cooperative polysialylation of the neural cell adhesion molecule by two polysialyltransferases, PST and STX [J].
Angata, K ;
Suzuki, M ;
Fukuda, M .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (43) :28524-28532
[2]   Valproate and valproate-analogues: Potent tools to fight against cancer [J].
Blaheta, RA ;
Nau, H ;
Michaelis, M ;
Cinatl, J .
CURRENT MEDICINAL CHEMISTRY, 2002, 9 (15) :1417-1433
[3]   Expression level of neural cell adhesion molecule (NCAM) inversely correlates with the ability of neuroblastoma cells to adhere to endothelium in vitro [J].
Blaheta, RA ;
Hundemer, M ;
Mayer, G ;
Vogel, JU ;
Kornhuber, B ;
Cinatl, J ;
Markus, BH ;
Driever, PH ;
Cinatl, J .
CELL COMMUNICATION AND ADHESION, 2002, 9 (03) :131-147
[4]   N-CAM modulates tumour-cell adhesion to matrix by inducing FGF-receptor signalling [J].
Cavallaro, U ;
Niedermeyer, J ;
Fuxa, M ;
Christofori, G .
NATURE CELL BIOLOGY, 2001, 3 (07) :650-657
[5]  
Cinatl J, 1999, INT J ONCOL, V15, P1001
[6]   Antitumor activity of sodium valproate in cultures of human neuroblastoma cells [J].
Cinatl, J ;
Cinatl, J ;
Scholz, M ;
Driever, PH ;
Henrich, D ;
Kabickova, H ;
Vogel, JU ;
Doerr, HW ;
Kornhuber, B .
ANTI-CANCER DRUGS, 1996, 7 (07) :766-773
[7]   Sodium valproate inhibits in vivo growth of human neuroblastoma cells [J].
Cinatl, J ;
Cinatl, J ;
Driever, PH ;
Kotchetkov, R ;
Pouckova, P ;
Kornhuber, B ;
Schwabe, D .
ANTI-CANCER DRUGS, 1997, 8 (10) :958-963
[8]  
Cinatl J, 2002, INT J ONCOL, V20, P97
[9]  
Daniel L, 2000, CANCER RES, V60, P80
[10]   A nude mice model of human rhabdomyosarcoma lung metastases for evaluating the role of polysialic acids in the metastatic process [J].
Daniel, L ;
Durbec, P ;
Gautherot, E ;
Rouvier, E ;
Rougon, G ;
Figarella-Branger, D .
ONCOGENE, 2001, 20 (08) :997-1004