PMID- 10697596
OWN - NLM
STAT- MEDLINE
DCOM- 20000316
LR  - 20071114
IS  - 0250-7005 (Print)
IS  - 0250-7005 (Linking)
VI  - 19
IP  - 6A
DP  - 1999 Nov-Dec
TI  - The role of oval cells and gap junctional intercellular communication in 
      hepatocarcinogenesis.
PG  - 4831-8
AB  - The role of oval cells, and Gap Junctional Intercellular Communication (GJIC) in 
      hepatic differentiation and neoplasia is controversial. Oval cells accumulate in 
      great number when hepatocyte regeneration is blocked following massive 
      hepatotoxicity or after treatment with some hepatocarcinogens. This suggests oval 
      cells are facultative stem cells or close progeny of liver stem cells that are 
      activated only under specific conditions. Studies with oval cell lines clearly 
      indicate that they can differentiate into hepatocytes and that neoplastic 
      derivatives of oval cells can produce hepatocellular and biliary neoplasms. 
      Because hepatocytes express Cx32 and biliary cells express Cx43, the 
      differentiation of oval cells into hepatocytes or In addition, because Cx32 
      hemichannels and Cx43 hemichannels cannot form heterotypic patent channels, the 
      type of connexin expressed by the differentiating oval cell will determine 
      whether it communicates with hepatocytes or biliary epithelial cells, 
      respectively. This communication may be necessary for the further differentiation 
      and regulated growth of the differentiating oval cells and impairment of this 
      GJIC may contribute to the formation of hepatocellular and cholangiocellular 
      neoplasms. The type of connexin expressed may also determine the susceptibility 
      of the differentiating oval cells to the various types of rodent liver tumor 
      promoters. Thus, three major points have been developed here. First, Cx32 or Cx43 
      expression and GJIC with hepatocytes or biliary epithelial cells, respectively, 
      may determine the final differentiated fate of oval cells. Secondly, blocked GJIC 
      may determine whether oval cells progress to hepatocellular or cholangiocellular 
      carcinoma. Lastly, the ability of tumor promoters to block Cx32 or Cx43-mediated 
      GJIC in differentiating oval cells may determine whether these agents promote the 
      formation of hepatocellular or cholangiocellular carcinomas. Thus, GJIC may be 
      the key factor in the differentiation of oval cells and blocked GJIC may promote 
      their neoplastic transformation in a lineage-specific manner. In this chapter, we 
      have outlined several new hypotheses on the role of oval cells and GJIC in 
      hepatocarcinogenesis. We hope that other investigators will consider our ideas, 
      but realize these views will be contentious to many. Our intent, however, was to 
      stimulate discussion and debate, even argument, because truth often arises amidst 
      controversy and may be found in the most peculiar places.
FAU - Ruch, R J
AU  - Ruch RJ
AD  - Department of Pathology, Medical College of Ohio, Toledo 43614, USA. 
      rruch@mco.edu
FAU - Trosko, J E
AU  - Trosko JE
LA  - eng
GR  - CA-24011/CA/NCI NIH HHS/United States
GR  - CA-57612/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PT  - Review
PL  - Greece
TA  - Anticancer Res
JT  - Anticancer research
JID - 8102988
SB  - IM
MH  - Animals
MH  - *Cell Communication
MH  - Cell Differentiation
MH  - Cell Division
MH  - *Gap Junctions
MH  - Liver Neoplasms, Experimental/*pathology
RF  - 78
EDAT- 2000/03/04 09:00
MHDA- 2000/03/18 09:00
CRDT- 2000/03/04 09:00
PHST- 2000/03/04 09:00 [pubmed]
PHST- 2000/03/18 09:00 [medline]
PHST- 2000/03/04 09:00 [entrez]
PST - ppublish
SO  - Anticancer Res. 1999 Nov-Dec;19(6A):4831-8.