Levels of vitamin K, immunoreactive prothrombin, des-gamma-carboxy prothrombin and gamma-glutamyl carboxylase activity in hepatocellular carcinoma tissue.
To clarify the mechanism of production of des-gamma-carboxy (abnormal) prothrombin (DCP) by hepatocellular carcinoma (HCC), we measured the levels of vitamin K, DCP, immunoreactive prothrombin and the activity of gamma-glutamyl carboxylase in liver tissues from HCC patients and in the medium of cultured human hepatoma cells. There was no significant difference in vitamin K (K1, MK-4) contents between HCC and non-HCC cirrhotic liver tissues. The activity of gamma-glutamyl carboxylase per unit amount of endogenous microsomal prothrombin precursor was decreased in HCC tissue compared with non-HCC liver tissue (positive plasma DCP: 335 +/- 72 vs 372 +/- 67, negative plasma DCP: 370 +/- 84 vs 393 +/- 56 nmol/min per mg prothrombin precursor, P > 0.05), although the total incorporation of 14COOH into microsomal precursor protein was higher in the former. By contrast, levels of DCP and immunoreactive prothrombin in HCC tissue were greater (P < 0.05) than those in non-HCC cirrhotic liver tissue. Furthermore, production of large amounts of immunoreactive prothrombin was observed in human hepatoma cells huH-1 and huH-2, which produced large amounts of DCP. These results suggest that there was excessive synthesis of prothrombin precursors by human HCC tissue and hepatoma cell lines huH-1 and huH-2. Thus, excessive synthesis of prothrombin precursors seems to be the main mechanism of DCP production by HCC.
Yamagata
H
H
Institute of Gastroenterology, Tokyo Women's Medical College, Japan.
Nakanishi
T
T
Furukawa
M
M
Okuda
H
H
Obata
H
H
D000368:Aged; D015415:Biomarkers; D019735:Carbon-Carbon Ligases; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008025:Ligases / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008113:Liver Neoplasms / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011498:Protein Precursors / Q000096:biosynthesis*; D011516:Prothrombin / Q000096:biosynthesis* / Q000378:metabolism*; D011863:Radioimmunoassay; D014407:Tumor Cells, Cultured; D014812:Vitamin K / Q000378:metabolism*
D015415:Biomarkers; D011498:Protein Precursors; D014812:Vitamin K; C008208:acarboxyprothrombin; D011516:Prothrombin; D008025:Ligases; D019735:Carbon-Carbon Ligases; C020660:glutamyl carboxylase