title: Effect of the three-dimensional organization of liver cells on the biogenesis of the γ-glutamyltransferase fraction pattern.
abstract: Context Four gamma-glutamyltransferase (GGT) fractions with different molecular weights (big-, medium-, small- and free-GGT) are detectable in human plasma. Objective Verify if liver cells can release all four GGT fractions and if the spatial cell organization influences their release. Methods Hepatoma (HepG2) and melanoma (Me665/2/60) cells were cultured as monolayers or spheroids. GGT released in culture media was analysed by gel-filtration chromatography. Results HepG2 and Me665/2/60 monolayers released the b-GGT fraction, while significative levels of s-GGT and f-GGT were detectable only in media of HepG2-spheroids. Bile acids alone or in combination with papain promoted the conversion of b-GGT in s-GGT or f-GGT, respectively. Conclusions GGT is usually released as b-GGT, while s-GGT and f-GGT are likely to be produced in the liver extracellular environment by the combined action of bile acids and proteases.
authors.affiliation: a Department of Translational Research and New Technologies in Medicine and Surgery , University of Pisa , Pisa , Italy ;
authors.forename: Alessandro
authors.initials: A
authors.lastname: Corti
authors.affiliation: a Department of Translational Research and New Technologies in Medicine and Surgery , University of Pisa , Pisa , Italy ;
authors.forename: Vanna
authors.initials: V
authors.lastname: Fierabracci
authors.affiliation: a Department of Translational Research and New Technologies in Medicine and Surgery , University of Pisa , Pisa , Italy ;
authors.forename: Laura
authors.initials: L
authors.lastname: Caponi
authors.affiliation: a Department of Translational Research and New Technologies in Medicine and Surgery , University of Pisa , Pisa , Italy ;
authors.forename: Aldo
authors.initials: A
authors.lastname: Paolicchi
authors.affiliation: a Department of Translational Research and New Technologies in Medicine and Surgery , University of Pisa , Pisa , Italy ;
authors.forename: Evelina
authors.initials: E
authors.lastname: Lorenzini
authors.affiliation: b Department of Surgical, Medical, Molecular Pathology and Emergency Medicine , University of Pisa , Pisa , Italy ;
authors.forename: Daniela
authors.initials: D
authors.lastname: Campani
authors.affiliation: a Department of Translational Research and New Technologies in Medicine and Surgery , University of Pisa , Pisa , Italy ;|c Fondazione G. Monasterio CNR-Regione Toscana , Pisa , Italy ;
authors.forename: Eugenia
authors.initials: E
authors.lastname: Belcastro
authors.affiliation: a Department of Translational Research and New Technologies in Medicine and Surgery , University of Pisa , Pisa , Italy ;|c Fondazione G. Monasterio CNR-Regione Toscana , Pisa , Italy ;
authors.forename: Maria
authors.initials: M
authors.lastname: Franzini
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002850:Chromatography, Gel; D006801:Humans; D008099:Liver / Q000166:cytology* / Q000201:enzymology*; D008113:Liver Neoplasms / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D008545:Melanoma / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D008970:Molecular Weight; D005723:gamma-Glutamyltransferase / Q000096:biosynthesis* / Q000378:metabolism
chemical_list: D005723:gamma-Glutamyltransferase
keywords: Bile acids; HepG2 cells; gel-filtration chromatography; liver parenchyma; spheroids