Ultrastructural characteristics of liver fluke associated human cholangiocarcinoma cell lines

The ultrastructure of a cholangiocarcinoma cell line (HuCCA-l) originally established from an intrahepatic bile duct tumor of a patient seropositive for a liver fluke infection was studied by scanning (SEM) and transmission (TEM) electron miscroscopy. With the SEM, the surface of HuCCA-1 cells were found to be covered with microvilli. The size of these microvilli varied from cell to cell and they were irregularly distributed. The TEM clearly revealed the presence of cytokeratin filaments, an intracytoplasmic lumen, tight junctions at the apices and desmosomes at the lateral surfaces of neighboring cells, all of which are characteristics of adenocarcinoma cell origin. However, the tumor mass that developed in a nude mouse following subcutaneous injection of these cells was found to exhibit some morphological changes. Specifically, about 20-30% of the tumor cells, particularly those lining the base of the tumor tubules, exhibited electron dense tonofilaments typical of squamous cells. However, this alteration was reversible as the cell line (HuCCA-1Nu) derived from this nude mouse-passage did not exhibit any characteristics reminiscent of squamous cells. These observations are consistent with those occasionally found in human cases reported previously by other investigators. Altogether, the data showed that squamous transformation of adenocarcinoma cells can occur under appropriate conditions. It further showed that reversion to adenocarcinoma cells can occur when the microenvironment is changed.