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Cellular origin of hepatocellular carcinomas.
1Department of Pathology and Laboratory Medicine, Division of Experimental Pathology, MC-151, Albany Medical College, 47 New Scotland Avenue, Albany, NY 12208-3479, USA. sells@mail.amc.edu
Seminars in Cell & Developmental Biology
|December 7, 2002
Summary
Different liver cell types respond to specific carcinogens, leading to various liver cancers. Research identifies four distinct hepatic cell levels and their roles in hepatocarcinogenesis, including potential bone marrow origins for stem cells.
Area of Science:
- Hepatology
- Carcinogenesis
- Cell Biology
Background:
- The liver contains multiple cell types capable of initiating cancer.
- Understanding the cell of origin for different liver cancers is crucial for targeted therapies.
Purpose of the Study:
- To delineate the specific hepatic cell lineages involved in various hepatocarcinogenesis models.
- To investigate the potential extrahepatic origin of liver stem cells.
Main Methods:
- Review of established hepatocarcinogenesis models using specific chemical carcinogens (diethylnitrosamine, N-2-acetylaminofluorene).
- Analysis of liver fluke-induced models and dimethylnitrosamine exposure in hamsters.
- Examination of choline deficiency models for hepatocellular carcinoma (HCC) induction.
- Integration of data from bone marrow transplantation studies indicating donor cell markers in recipient hepatocytes.
Main Results:
- Mature hepatocytes respond to diethylnitrosamine (DEN).
- Bile duct progenitor cells are implicated in cholangiocellular carcinomas.
- Ductular 'bipolar' progenitor cells give rise to HCC under N-2-acetylaminofluorene regimens.
- Periductular stem cells are the origin of HCC in choline deficiency models, with potential bone marrow origin.
Conclusions:
- Four distinct hepatic cell levels serve as origins for different types of liver cancer.
- Periductular stem cells may originate from extrahepatic sources, such as bone marrow.