Stem-like Cells in Human Hepatoblastoma

Abstract

S U M M A R YHepatoblastoma is a pediatric liver tumor with epithelial components resembling embryonal and fetal liver cells. The existence of teratoid hepatoblastoma suggests the presence of stem cells in hepatoblastoma. The aim of this study was to analyze the expression of stem cell markers in hepatoblastomas. We studied specimens from 10 hepatoblastomas. Five of the hepatoblastomas were of epithelial and five of mixed type. Immunohistochemistry (IHC) for the stem cell markers CD34, Thy1, c-kit, and the hepatic or biliary lineage markers CK-18, OCH, CK-7, and CD56 was performed. Double IHC for stem cell and lineage markers was used to identify putative liver stem cells. The different markers showed distinct distributions on the tumor cells. Cells in atypical ducts were found to express simultaneously stem cell markers and hepatocytic or biliary lineage markers. Other cells in connective tissue showed c-kit expression, but not hepatic or biliary marker expression. The data show the presence of different cell populations bearing stem cell markers in human hepatoblastoma. Ductal cells co-expressing stem cell markers and hepatic lineage markers phenotypically resemble hepatic stem-like cells. These findings support the thesis that stem cells play a role in the histogenesis of hepatoblastoma.

CD133 positive hepatocellular carcinoma cells possess high capacity for tumorigenicity

“…21 By immunostaining, a group of stem-like cells, with surface marker pattern similar to normal liver progenitors, had been revealed in hepatoblastoma. 24 In the present study, we demonstrated that CD133 was expressed in SMMC-7721 cells, and also consistently present in other human HCC cell lines we examined: BEL-7402, Hep3B, Huh-7, MHCC-LM3, MHCC-97L (data not shown). Although long-term cultured cell lines are thought to lose some properties of parental tumor and consist of less divergent population, the cell heterogeneity still exists.…”

Liver stem cells and their implication in hepatocellular and cholangiocarcinoma

“…Also in hepatoblastomas, the most common liver tumour in childhood, cells resembling progenitor cells have been noted (Ruck et al, 1996;Xiao et al, 2003;Fiegel et al, 2004). This tumour is widely believed to be of stem cell origin, as it can be composed of both epithelial and mesenchymal tissue components.…”

Stem cells in liver regeneration, fibrosis and cancer: the good, the bad and the ugly

“…Cells with an HPC phenotype have also been noted in a relatively rare subset of hepatic malignancies where there are clearly two major components, an HCC component and a cholangiocarcinoma component, again suggestive of an origin from a bipotential progenitor [138]. Cells resembling HPCs (eg OV.1 + or OV-6 + ; see Table 2) have also been noted in hepatoblastoma [139][140][141][142], the most common liver tumour in childhood, likely to be stem cell-derived given there can be both epithelial and mesenchymal tissue components. Hepatoblastomas can even have structures mimicking embryonic intrahepatic bile duct formation, with the formation ductal plate-like structures [143,144].…”