Bone marrow-derived stem cells and hepatocarcinogenesis in hepatitis B virus transgenic mice

Michele Barone, Maria Principia Scavo, Eugenio Maiorano, Alfredo Di Leo, Antonio Francavilla

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)243-250
Number of pages8
JournalDigestive and Liver Disease
Volume46
Issue number3
DOIs
Publication statusPublished - Mar 2014

Fingerprint

Hepatitis B Surface Antigens
Hepatitis B virus
Transgenic Mice
Stem Cells
Bone Marrow
Hepatocyte Nuclear Factor 1
Y Chromosome
Genes
Hepatocytes
Liver
Proteins
Neoplastic Stem Cells
Cell Fusion
Bone Marrow Cells

Keywords

  • Cell fusion
  • Cell homing
  • Cell mimicry
  • Microenvironment

ASJC Scopus subject areas

  • Gastroenterology
  • Hepatology

Cite this

Bone marrow-derived stem cells and hepatocarcinogenesis in hepatitis B virus transgenic mice. / Barone, Michele; Scavo, Maria Principia; Maiorano, Eugenio; Di Leo, Alfredo; Francavilla, Antonio.

In: Digestive and Liver Disease, Vol. 46, No. 3, 03.2014, p. 243-250.

Research output: Contribution to journalArticle

Barone, Michele ; Scavo, Maria Principia ; Maiorano, Eugenio ; Di Leo, Alfredo ; Francavilla, Antonio. / Bone marrow-derived stem cells and hepatocarcinogenesis in hepatitis B virus transgenic mice. In: Digestive and Liver Disease. 2014 ; Vol. 46, No. 3. pp. 243-250.
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N2 - 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.

AB - 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.

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