Document Detail

Intrahepatic cholangiocarcinoma can arise from Notch-mediated conversion of hepatocytes.
MedLine Citation:
PMID:  23023701     Owner:  NLM     Status:  MEDLINE    
Intrahepatic cholangiocarcinoma (ICC) is the second most common primary malignancy in the liver. ICC has been classified as a malignant tumor arising from cholangiocytes; however, the co-occurrence of ICC and viral hepatitis suggests that ICC originates in hepatocytes. In order to determine the cellular origin of ICC, we used a mouse model of ICC in which hepatocytes and cholangiocytes were labeled with heritable, cell type–specific reporters. Our studies reveal that ICC is generated by biliary lineage cells derived from hepatocytes, rather than cholangiocytes. Additionally, we found that Notch activation is critical for hepatocyte conversion into biliary lineage cells during the onset of ICC and its subsequent malignancy and progression. These findings will help to elucidate the pathogenic mechanism of ICC and to develop therapeutic strategies for this refractory disease.
Sayaka Sekiya; Atsushi Suzuki
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of clinical investigation     Volume:  122     ISSN:  1558-8238     ISO Abbreviation:  J. Clin. Invest.     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-12-26     Completed Date:  2013-01-15     Revised Date:  2013-07-11    
Medline Journal Info:
Nlm Unique ID:  7802877     Medline TA:  J Clin Invest     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3914-8     Citation Subset:  AIM; IM    
Division of Organogenesis and Regeneration, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
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MeSH Terms
Cell Transformation, Neoplastic / genetics,  metabolism*,  pathology
Cholangiocarcinoma / etiology,  genetics,  metabolism*,  pathology
Genes, Reporter
Hepatitis, Viral, Animal / metabolism,  pathology
Hepatocytes / metabolism*,  pathology
Liver Neoplasms / etiology,  genetics,  metabolism*,  pathology
Mice, Transgenic
Neoplasm Proteins / genetics,  metabolism*
Receptors, Notch / genetics,  metabolism*
Reg. No./Substance:
0/Neoplasm Proteins; 0/Receptors, Notch
Comment In:
Hepatology. 2013 Apr;57(4):1668-71   [PMID:  23390051 ]

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