Stem-like cells in hepatitis B virus–associated cirrhotic livers and adjacent tissue to hepatocellular carcinomas possess the capacity of tumorigenicity
Article first published online: 7 MAY 2008
© 2008 The Authors. Journal compilation © 2008 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd
Journal of Gastroenterology and Hepatology
Volume 23, Issue 8pt1, pages 1280–1286, August 2008
How to Cite
Sun, Y.-L., Yin, S.-Y., Xie, H.-Y., Zhou, L., Xue, F., Wu, L.-M., Gao, F. and Zheng, S.-S. (2008), Stem-like cells in hepatitis B virus–associated cirrhotic livers and adjacent tissue to hepatocellular carcinomas possess the capacity of tumorigenicity. Journal of Gastroenterology and Hepatology, 23: 1280–1286. doi: 10.1111/j.1440-1746.2008.05342.x
- Issue published online: 31 JUL 2008
- Article first published online: 7 MAY 2008
- Accepted for publication 18 October 2007.
- Hepatitis B virus;
- hepatocellular carcinoma;
- stem cells;
Background and Aim: 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.
Conclusion: 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.