Stem-like cells in hepatitis B virus-associated cirrhotic livers and adjacent tissue to hepatocellular carcinomas possess the capacity of tumorigenicity.
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.
Sun
Yu-Ling
YL
Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Hangzhou, China.
Yin
Sheng-Yong
SY
Xie
Hai-Yang
HY
Zhou
Lin
L
Xue
Fei
F
Wu
Li-Ming
LM
Gao
Feng
F
Zheng
Shu-Sen
SS
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*
D014408:Biomarkers, Tumor