title: Stem-like cells in hepatitis B virus-associated cirrhotic livers and adjacent tissue to hepatocellular carcinomas possess the capacity of tumorigenicity.
abstract: OBJECTIVE
  Recent investigations demonstrate that adult stem cells may be targets for malignant transformation and that the stem-like cells in diseased livers possess the capacity of tumorigenicity in animal models. The aim of this study is to examine expression patterns of stem-cell markers in hepatitis B virus-associated cirrhotic livers and hepatocellular carcinomas (HCC), and to investigate the stem-like cell capacity of tumorigenicity in these tissues.
  
  
  METHODS
  Twenty surgically resected HCCs and corresponding adjacent tissues as well as 10 cirrhotic liver tissues were collected and immunohistochemical staining were performed to detect the expression of CD34, Thy-1, CD133, and c-kit. Then the non-cancerous tissues were transplanted into immunodeficient mice and the characteristics of the cells from primary tissue cultures were explored in vitro.
  
  
  RESULTS
  Immunohistochemical analysis characterized different expression patterns of stem-cell markers among these tissues. First, CD34 and Thy-1 expression was identified in proliferating bile ductules and it represented hepatic progenitor cells; CD133 and c-kit-positive cells were observed in the parenchyma of these tissues, and some of them were characterized as intermediate hepatocytes morphologically and spatially. Second, in two groups including three mice transplanted with tissues adjacent to HCC-initiated tumors, CD133 and c-kit expression was detected. Finally, our study also indicated that stem-like cells from tissue could express hepatic-lineage markers and possessed great capacities to proliferate, self-renew, and form clones in vitro.
  
  
  CONCLUSIONS
  Our results suggest that the stem-like cells in cirrhotic livers possess the capacity of tumorigenicity and may contain candidates for HCC cancer stem cells.
authors.affiliation: Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Hangzhou, China.
authors.forename: Yu-Ling
authors.initials: YL
authors.lastname: Sun
authors.forename: Sheng-Yong
authors.initials: SY
authors.lastname: Yin
authors.forename: Hai-Yang
authors.initials: HY
authors.lastname: Xie
authors.forename: Lin
authors.initials: L
authors.lastname: Zhou
authors.forename: Fei
authors.initials: F
authors.lastname: Xue
authors.forename: Li-Ming
authors.initials: LM
authors.lastname: Wu
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
authors.forename: Shu-Sen
authors.initials: SS
authors.lastname: Zheng
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000032:analysis; D006528:Carcinoma, Hepatocellular / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D019694:Hepatitis B, Chronic / Q000150:complications*; D006801:Humans; D007150:Immunohistochemistry; D008103:Liver Cirrhosis / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D008113:Liver Neoplasms / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor