| Histological and culture studies with respect to ABCG2 expression support the existence of a cancer cell hierarchy in human hepatocellular carcinoma. | |
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MedLine Citation:
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PMID: 17456779 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Yoh Zen; Takahiko Fujii; Seiichi Yoshikawa; Hiroyuki Takamura; Takashi Tani; Tetsuo Ohta; Yasuni Nakanuma |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: The American journal of pathology Volume: 170 ISSN: 0002-9440 ISO Abbreviation: Am. J. Pathol. Publication Date: 2007 May |
Date Detail:
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Created Date: 2007-04-25 Completed Date: 2007-06-26 Revised Date: 2009-11-18 |
Medline Journal Info:
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Nlm Unique ID: 0370502 Medline TA: Am J Pathol Country: United States |
Other Details:
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Languages: eng Pagination: 1750-62 Citation Subset: AIM; IM |
Affiliation:
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Department of Human Pathology, Kanazawa University Graduate School of Medicine, 13-1 Takaramachi, Kanazawa 920-8640, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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ATP-Binding Cassette Transporters
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biosynthesis* Adult Aged Carcinoma, Hepatocellular / metabolism, pathology* Cell Line, Tumor Female Fluorescent Antibody Technique Hepatocytes / metabolism, pathology* Humans Immunohistochemistry Liver Neoplasms / metabolism, pathology* Male Middle Aged Neoplasm Proteins / biosynthesis* Neoplastic Stem Cells / metabolism, pathology* Reverse Transcriptase Polymerase Chain Reaction |
| Chemical | |
Reg. No./Substance:
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0/ABCG2 protein, human; 0/ATP-Binding Cassette Transporters; 0/Neoplasm Proteins |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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