title: Bone marrow-derived stem cells and hepatocarcinogenesis in hepatitis B virus transgenic mice.
abstract: BACKGROUND
  Several studies have demonstrated that cancer can develop with the contribution of bone marrow-derived cancer stem cells. We evaluated the possible involvement of bone marrow-derived stem cells in hepatocarcinogenesis in a hepatitis B virus (HBV) transgenic mouse model.
  
  
  METHODS
  Bone marrow cells from wild type male mice were transplanted into sublethally irradiated, female, HBV transgenic mice with hepatocarcinoma nodules. Four months later, liver tissue was examined to localize neoplastic nodules/foci and characterize cells by evaluating the Y-chromosome and the hepatocyte lineage marker hepatocyte nuclear factor-1 (HNF1), as well as the HBsAg encoding gene (HBs-Eg) and HBsAg protein (HBs-Pr) (present only in cells of female origin).
  
  
  RESULTS
  Hepatocytes were HBs-Eg/HBs-Pr-positive in "normal" tissue, while resulted only HBs-Eg-positive in regenerative areas. Neoplastic foci/nodules were both HBs-Eg/HBs-Pr-negative. In the liver, 19 ± 5% of cells were Y-chromosome-positive and about one fifth were HNF1-positive. Y-chromosome and HBs-Eg colocalized in HNF1-positive cells. Y-chromosome-positive cells never localized in neoplastic foci/nodules (HBs-Pr/HBs-Eg-negative).
  
  
  CONCLUSIONS
  Bone marrow-derived stem cells participate in the hepatic regenerative process but not in neoplastic growth. Simultaneous detection of both Y-chromosome and HBs-Eg in the nucleus of an HNF1-positive cell (hepatocyte) demonstrates a phenomenon of cell fusion.
authors.affiliation: Section of Gastroenterology, Department of Emergency and Organ Transplantation (DETO), University of Bari, Bari, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Barone
authors.affiliation: Section of Gastroenterology, Department of Emergency and Organ Transplantation (DETO), University of Bari, Bari, Italy.
authors.forename: Maria Principia
authors.initials: MP
authors.lastname: Scavo
authors.affiliation: Section of Pathological Anatomy, Department of Pathological Anatomy and Genetics, University of Bari, Bari, Italy.
authors.forename: Eugenio
authors.initials: E
authors.lastname: Maiorano
authors.affiliation: Section of Gastroenterology, Department of Emergency and Organ Transplantation (DETO), University of Bari, Bari, Italy.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Di Leo
authors.affiliation: IRCCS "S. De Bellis" Castellana Grotte, Bari, Castellana Grotte, Italy. Electronic address: direzionescientifica@irccsdebellis.it.
authors.forename: Antonio
authors.initials: A
authors.lastname: Francavilla
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism*; D016026:Bone Marrow Transplantation; D063646:Carcinogenesis; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D006509:Hepatitis B; D006514:Hepatitis B Surface Antigens / Q000235:genetics* / Q000378:metabolism; D022781:Hepatocytes / Q000378:metabolism*; D017404:In Situ Hybridization, Fluorescence; D008113:Liver Neoplasms / Q000378:metabolism*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D013234:Stem Cells / Q000378:metabolism*; D014998:Y Chromosome / Q000378:metabolism
chemical_list: D006514:Hepatitis B Surface Antigens
keywords: Cell fusion; Cell homing; Cell mimicry; Microenvironment