title: Sialic acid metabolic engineering: a potential strategy for the neuroblastoma therapy.
abstract: BACKGROUND
  Sialic acids (Sia) represent negative-charged terminal sugars on most glycoproteins and glycolipids on the cell surface of vertebrates. Aberrant expression of tumor associated sialylated carbohydrate epitopes significantly increases during onset of cancer. Since Sia contribute towards cell migration ( =  metastasis) and to chemo- and radiation resistance. Modulation of cellular Sia concentration and composition poses a challenge especially for neuroblastoma therapy, due to the high heterogeneity and therapeutic resistance of these cells. Here we propose that Metabolic Sia Engineering (MSE) is an effective strategy to reduce neuroblastoma progression and metastasis.
  
  
  METHODS
  Human neuroblastoma SH-SY5Y cells were treated with synthetic Sia precursors N-propanoyl mannosamine (ManNProp) or N-pentanoyl mannosamine (ManNPent). Total and Polysialic acids (PolySia) were investigated by high performance liquid chromatography. Cell surface polySia were examined by flow-cytometry. Sia precursors treated cells were examined for the migration, invasion and sensitivity towards anticancer drugs and radiation treatment.
  
  
  RESULTS
  Treatment of SH-SY5Y cells with ManNProp or ManNPent (referred as MSE) reduced their cell surface sialylation significantly. We found complete absence of polysialylation after treatment of SH-SY5Y cells with ManNPent. Loss of polysialylation results in a reduction of migration and invasion ability of these cells. Furthermore, radiation of Sia-engineered cells completely abolished their migration. In addition, MSE increases the cytotoxicity of anti-cancer drugs, such as 5-fluorouracil or cisplatin.
  
  
  CONCLUSIONS
  Metabolic Sia Engineering (MSE) of neuroblastoma cells using modified Sia precursors reduces their sialylation, metastatic potential and increases their sensitivity towards radiation or chemotherapeutics. Therefore, MSE may serve as an effective method to treat neuroblastoma.
authors.affiliation: Institute for Physiological Chemistry, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany.
authors.forename: Vinayaga S
authors.initials: VS
authors.lastname: Gnanapragassam
authors.affiliation: Institute for Physiological Chemistry, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany.
authors.forename: Kaya
authors.initials: K
authors.lastname: Bork
authors.affiliation: Institute of Biochemistry, Faculty of Medicine, University of Giessen, Giessen, Germany.
authors.forename: Christina E
authors.initials: CE
authors.lastname: Galuska
authors.affiliation: Institute of Biochemistry, Faculty of Medicine, University of Giessen, Giessen, Germany.
authors.forename: Sebastian P
authors.initials: SP
authors.lastname: Galuska
authors.affiliation: Institute for Physiological Chemistry, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany.
authors.forename: Dagobert
authors.initials: D
authors.lastname: Glanz
authors.affiliation: Institute for Physiological Chemistry, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany.
authors.forename: Manimozhi
authors.initials: M
authors.lastname: Nagasundaram
authors.affiliation: Clinic of Radiotherapy, University Hospital Halle, Halle (Saale), Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Bache
authors.affiliation: Clinic of Radiotherapy, University Hospital Halle, Halle (Saale), Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Vordermark
authors.affiliation: Octapharma R&D, Molecular Biochemistry, Berlin, Germany.
authors.forename: Guido
authors.initials: G
authors.lastname: Kohla
authors.affiliation: Octapharma R&D, Molecular Biochemistry, Berlin, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Kannicht
authors.affiliation: Institute of Biochemistry, University of Kiel, Kiel, Germany.
authors.forename: Roland
authors.initials: R
authors.lastname: Schauer
authors.affiliation: Institute for Physiological Chemistry, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany.
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Horstkorte
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D018432:Drug Resistance, Multiple / Q000187:drug effects; D005434:Flow Cytometry; D006595:Hexosamines / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D060847:Metabolic Engineering; D019158:N-Acetylneuraminic Acid / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D009447:Neuroblastoma / Q000188:drug therapy / Q000378:metabolism*; D011836:Radiation Tolerance / Q000187:drug effects; D012794:Sialic Acids / Q000378:metabolism / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D006595:Hexosamines; C116506:N-pantanoylmannosamine; D012794:Sialic Acids; C021319:polysialic acid; D019158:N-Acetylneuraminic Acid