Fatty change in human hepatocellular carcinoma cell lines derived from patients with antibodies to hepatitis C virus.

BACKGROUND/AIMS: Evidence suggesting a relationship between fatty change in normal or malignant hepatocytes and hepatitis C virus has gradually accumulated, but less is known about the relationship between cell proliferation and fatty change in human hepatocellular carcinoma.

METHODOLOGY

We studied the latter issue in two human hepatocellular carcinoma cell lines (OCUH-16 and Nuk-1) derived from hepatitis C virus-associated tumors. We examined the relationship between degree of fatty change assessed by oil-red-O staining and electron microscopy, actively proliferating cells counted using a monoclonal antibody to MIB-1 protein, and apoptotic cells counted using DNA nick-end labeling in the above two hepatocellular carcinoma cell lines with time lapse.

RESULTS

On day 1 in culture, fatty change was present randomly in cytoplasm of some Nuk-1 cells, but was not found in OCUH-16 cells. Over time, fat droplets were found more frequently in large hepatocellular carcinoma cells in both Nuk-1 and OCUH-16 lines. Most of these cells were located in the periphery of hepatocellular carcinoma cell nests or islands as opposed to the small hepatocellular carcinoma cells located in the centers of nests in both lines. According to MIB-1 staining, these small cells proliferate more actively than the large, peripherally located hepatocellular carcinoma cells. Only a few apoptotic hepatocellular carcinoma cells were detected during culture.

CONCLUSIONS

Fatty change in large hepatocellular carcinoma cells seems to be associated with less proliferative activity than was seen in small hepatocellular carcinoma cells without fatty change, located in more centrally cell nests, in these hepatocellular carcinoma cell lines.