title: alpha2,6-Sialyltransferase gene transfection into a human glioma cell line (U373 MG) results in decreased invasivity.
abstract: Glycosyltransferase gene transfection into cell lines has been an approach used successfully to elucidate the functional role of cell surface glycoconjugates. We have transfected the rat CMP-NeuAc:Galbeta1,4GlcNAc alpha2,6-sialyltransferase (EC 2.4.99.1) gene into a human, tumorigenic, glioma cell line, U373 MG. This transfection led to a marked inhibition of invasivity, alterations in adhesivity to fibronectin and collagen matrices, and inappropriately sialylated alpha3beta1 integrin. Adhesion-mediated protein tyrosine phosphorylation was reduced in the transfectants despite increased expression of focal adhesion kinase, p125fak. Furthermore, the transfectants showed a distinct cell morphology, an increased number of focal adhesion sites, and different sensitivity to cytochalasin D treatment than control U373 MG cells. These results suggest that inappropriate sialylation of cell surface glycoconjugates, such as integrins, can change focal adhesion as well as adhesion-mediated signal transduction and block glioma cell invasivity in vitro.
authors.affiliation: Chicago Institute for Neurosurgery and Neuroresearch, Illinois, U.S.A.
authors.forename: H
authors.initials: H
authors.lastname: Yamamoto
authors.forename: Y
authors.initials: Y
authors.lastname: Kaneko
authors.forename: A
authors.initials: A
authors.lastname: Rebbaa
authors.forename: E G
authors.initials: EG
authors.lastname: Bremer
authors.forename: J R
authors.initials: JR
authors.lastname: Moskal
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D002448:Cell Adhesion / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000378:metabolism; D003001:Cloning, Molecular; D003094:Collagen / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D005910:Glioma; D006801:Humans; D039201:Integrin alpha3beta1; D016023:Integrins / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000503:physiopathology*; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D051381:Rats; D011972:Receptor, Insulin / Q000378:metabolism; D017474:Receptors, Laminin / Q000378:metabolism; D012794:Sialic Acids / Q000378:metabolism; D012799:Sialyltransferases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000737:chemistry / Q000201:enzymology; D014443:Tyrosine / Q000378:metabolism; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase
chemical_list: D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D005353:Fibronectins; D039201:Integrin alpha3beta1; D016023:Integrins; D017474:Receptors, Laminin; D012794:Sialic Acids; D014443:Tyrosine; D003094:Collagen; D012799:Sialyltransferases; D011505:Protein-Tyrosine Kinases; D011972:Receptor, Insulin; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496050:PTK2 protein, human; C496052:Ptk2 protein, rat; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase