Valproic acid modulates NCAM polysialylation and polysialyltransferase mRNA expression in human tumor cells.
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, VPA blocked the adhesion of several neuroectodermal tumor cell lines to human umbilical vein endothelial cells. Furthermore, VPA induced intracellular PSA accumulation and enhanced expression of PSA-NCAM on the cell surface. Using a semiquantitative RT-PCR strategy, VPA 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.
Beecken
Wolf-Dietrich
WD
Johann Wolfgang Goethe-Universitätsklinik, Zentrum der Chirurgie, Klinik für Urologie und KinderurologieWissenschaftliches LaborHaus 23 A, EG 7, Theodor-Stern-Kai 7, Frankfurt am Main D-60590, Germany.
Engl
Tobias
T
Ogbomo
Henry
H
Relja
Borna
B
Cinatl
Jindrich
J
Bereiter-Hahn
Jürgen
J
Oppermann
Elsie
E
Jonas
Dietger
D
Blaheta
Roman A
RA
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor / Q000378:metabolism*; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects; D042783:Endothelial Cells / Q000502:physiology; D006801:Humans; D019006:Neural Cell Adhesion Molecules / Q000378:metabolism*; D012333:RNA, Messenger / Q000187:drug effects; D012794:Sialic Acids / Q000378:metabolism*; D012799:Sialyltransferases / Q000187:drug effects* / Q000502:physiology; D015854:Up-Regulation / Q000187:drug effects; D014635:Valproic Acid / Q000494:pharmacology*
D000970:Antineoplastic Agents; D019006:Neural Cell Adhesion Molecules; D012333:RNA, Messenger; D012794:Sialic Acids; C021319:polysialic acid; D014635:Valproic Acid; C046778:CMP-N-acetylneuraminate-poly-alpha-2,8-sialosyl sialyltransferase; D012799:Sialyltransferases