γ-Glutamyl transpeptidase overexpression increases metastatic growth of B16 melanoma cells in the mouse liver

• DOI: 10.1053/jhep.2002.30277
• Publication Date: 2002-08-25T03:46:10Z
• Authors: Elena Obrador; Julian Carretero; Angel Ortega; Ignacio Medina; Vicente Rodilla; José A. Pellicer; José M. Estrela
• Keywords: Buthionine sulfoximine; Gamma-glutamyltransferase

B16 melanoma (B16M) cells with high glutathione (GSH) content show rapid proliferation in vitro and metastatic activity the liver vivo . γ-Glutamyl transpeptidase (GGT)-mediated extracellular GSH cleavage intracellular synthesis were studied B16M (F10) low (F1) potential. GGT was modified by transfection human gene (B16MF1/Tet-GGT cells) or acivicin-induced inhibition. B16MF1/Tet-GGT B16MF10 exhibited higher (35 ± 6 40 5 nmol/10 cells, respectively) (89 9 37 7 mU/10 as compared ( P < .05) B16MF1 (10 3 nmol 4 mU GGT/10 cells). Metastasis (number of foci/100 mm liver) increased pretreated ester (˜3-fold, .01), decreased inhibitor L-buthionine (S,R)-sulphoximine (˜5-fold 2-fold, respectively, .01). Liver, kidney, brain, lung, erythrocyte B16MF1/Tet-GGT- B16MF10-bearing mice B16MF1- non-tumor-bearing mice. Organic anion transporting polypeptide 1-independent sinusoidal efflux from hepatocytes (˜2-fold, .01) Our results indicate that tumor an intertissue flow can regulate their growth liver.