Document Detail

Histological and culture studies with respect to ABCG2 expression support the existence of a cancer cell hierarchy in human hepatocellular carcinoma.
MedLine Citation:
PMID:  17456779     Owner:  NLM     Status:  MEDLINE    
In this study, we examined the possible involvement of progenitor cells in the carcinogenesis of human hepatocellular carcinoma (HCC) using tissue specimens and cell lines. We used ATP-binding cassette transporter ABCG2 as a progenitor cell marker. Immunohistochemically, ABCG2(+) hepatocytes were observed in the periportal areas of the dysplastic nodule, and ABCG2(+) cancer cells were also scattered or focally clustered in HCC. We sorted the cultured HCC cells (HuH7 and PLC5) into ABCG2(+) and ABCG2(-) subpopulations and then subcultured them for 4 weeks. ABCG2(+) cells could generate ABCG2(+) and ABCG2(-) progenies during subculture, whereas ABCG2(-) cells bore only ABCG2(-) cells, suggesting that a cancer cell hierarchy with reference to ABCG2 exists in HCC cells and that ABCG2(+) cells reside at the higher rank in that hierarchy. Interestingly, other progenitor cell markers including cytokeratin 19 and alpha-fetoprotein were mainly expressed in ABCG2(+) subpopulations. Conversely, albumin expression was more intense in ABCG2(-) cells. In addition, the expression patterns of transcription factors (GATA6, CCAAT/enhancer-binding protein alpha, and CCAAT/enhancer-binding protein beta) in ABCG2(+) and ABCG2(-) cells resembled those during normal liver development. In conclusion, this study suggests that cancer cells with ABCG2 expression might play a central role in hepatocarcinogenesis and the maintenance of the cancer cell hierarchy of human HCC.
Yoh Zen; Takahiko Fujii; Seiichi Yoshikawa; Hiroyuki Takamura; Takashi Tani; Tetsuo Ohta; Yasuni Nakanuma
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  The American journal of pathology     Volume:  170     ISSN:  0002-9440     ISO Abbreviation:  Am. J. Pathol.     Publication Date:  2007 May 
Date Detail:
Created Date:  2007-04-25     Completed Date:  2007-06-26     Revised Date:  2013-06-06    
Medline Journal Info:
Nlm Unique ID:  0370502     Medline TA:  Am J Pathol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1750-62     Citation Subset:  AIM; IM    
Department of Human Pathology, Kanazawa University Graduate School of Medicine, 13-1 Takaramachi, Kanazawa 920-8640, Japan.
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MeSH Terms
ATP-Binding Cassette Transporters / biosynthesis*
Carcinoma, Hepatocellular / metabolism,  pathology*
Cell Line, Tumor
Fluorescent Antibody Technique
Hepatocytes / metabolism,  pathology*
Liver Neoplasms / metabolism,  pathology*
Middle Aged
Neoplasm Proteins / biosynthesis*
Neoplastic Stem Cells / metabolism,  pathology*
Reverse Transcriptase Polymerase Chain Reaction
Reg. No./Substance:
0/ABCG2 protein, human; 0/Neoplasm Proteins

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