title: Early fibrosis inhibits hepatocellular carcinoma mediated by free radical effects.
abstract: We studied the in-vitro/in-vivo interactions between HCC/HSCs in early and advanced fibrosis-models. Hep3B-mono-cultures secreted high levels of αFetoProtein (αFP). Human-HSCs co-cultured with Hep3B-cells significantly decreased αFP and increased their apoptosis. Confocal-microscopy demonstrated Hep3B-phagocytosis inside the HSCs suggesting a direct cellular-contact mediating anti-tumor effect. Leptin-activated HSCs further suppressed Hep3B-cells with increased ROS and decreased GSH. Following intrahepatic-Hep3B-cell injections, mice with established "advanced liver-fibrosis"; had higher tumor-size and αFP serum-levels as compared to non-fibrotic livers. Mice with "early liver-fibrosis", which initiated post tumor induction had a significant decrease in tumor and high Malondialdehyde (MDA) serum levels compared to advanced-fibrosis animals. At early-fibrosis stages, activated-HSCs express direct anti-tumor effects by phagocytosis and apoptosis of tumor-cells mediated by oxidative stress.
authors: Liver and Gastroenterology Units, Division of Medicine, Hadassah University Medical Center, Jerusalem, Israel.
authors: Nidal
authors: N
authors: Muhanna
authors: Sarit
authors: S
authors: Doron
authors: Lina
authors: L
authors: Abu-Tair
authors: Hiba
authors: H
authors: Zayyad
authors: Mahmud
authors: M
authors: Mahamid
authors: Johnny
authors: J
authors: Amer
authors: Rifaat
authors: R
authors: Safadi
mesh_terms: D000818:Animals; D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000503:physiopathology*; D002460:Cell Line; D018920:Coculture Techniques; D004195:Disease Models, Animal; D005609:Free Radicals / Q000378:metabolism*; D055166:Hepatic Stellate Cells / Q000276:immunology / Q000378:metabolism*; D022781:Hepatocytes / Q000378:metabolism*; D006801:Humans; D008103:Liver Cirrhosis / Q000503:physiopathology*; D008113:Liver Neoplasms / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D018384:Oxidative Stress; D010587:Phagocytosis; D000509:alpha-Fetoproteins / Q000378:metabolism
chemical_list: D005609:Free Radicals; D000509:alpha-Fetoproteins
keywords: Cirrhosis; Free radicals; Hep3B cells; Hepatic fibrosis; Homeostasis; Phagocytosis