S. Radaeva et P. Steinberg, PHENOTYPE AND DIFFERENTIATION PATTERNS OF THE OVAL CELL-LINES OC CDE-6 AND OC/CDE-22 DERIVED FROM THE LIVERS OF CARCINOGEN-TREATED RATS/, Cancer research, 55(5), 1995, pp. 1028-1038
An electron microscopic, immunocytochemical, and enzyme cytochemical a
nalysis of the previously established oval cell lines OC/CDE 6 and OC/
CDE 22 was performed to characterize the phenotype and differentiation
patterns of long-term cultures of oval cells, It was found that a-fet
oprotein, albumin, and cytokeratin 19 are present in all cultured cell
s, This indicates that oval cells constitute a population of immature
cells expressing features of the antigenic phenotype of both the hepat
ocyte and bile ductular cell lineages, An electron microscopic examina
tion revealed a gradual alteration in the ultrastructure of oval cells
toward hepatocyte-like cells. The majority of the oval cells were pos
itive for glucose-6-phosphatase activity, A particularly striking obse
rvation was that oval cells were heterogeneous in terms of peroxisome
content, Only about 50% of the oval cells had peroxisomes in the cytop
lasm, these cells probably being part of the hepatocyte lineage, The o
ther cultured cells did not reveal catalase activity and probably repr
esented cells committed to the bile ductular cell lineage, An addition
of clofibrate to the culture medium resulted in a marked peroxisome p
roliferation in all oval cells, indicating that oval cells might be ab
le to change their differentiation pathway depending on environmental
influence toward the hepatocyte lineage, It is most intriguing that in
oval cells with abundant cytoplasm peroxisome proliferation was accom
panied by proliferation of the smooth endoplasmic reticulum (this is a
morphological marker of mature hepatocytes), Taken together, our find
ings suggest that within the oval cell lines OC/CDE 6 and OC/CDE 22 ce
lls undergoing a morphological and functional differentiation along th
e hepatocyte and bile ductular cell lineages are present.