CYFRA 21-1 is released in TNF-α-induced apoptosis in the hepatocellular carcinoma cell line HuH-7

Many types of cancer cells widely express cytokeratin 19 (CK19). Clinical investigations have suggested that serum CYFRA 21-1, a fragment of CK19, is one of the most useful tumor markers. In the present study, we hypothesized that released CYFRA 21-1 is closely associated with cellular apoptosis during tumor growth. Apoptosis was induced by tumor necrosis factor-alpha (TNF-alpha) in the HuH-7 hepatocellular carcinoma cell line. Both TNF-alpha-treated and non-treated cells of HuH-7 were simultaneously examined by immunoradiometric assay, annexin-V apoptosis analysis, immunohistochemical staining and colorimetric protease measurement. Levels of CYFRA 21-1 increased significantly in TNF-alpha-treated cells displaying a high percentage of apoptosis, granular-like aggregation of CK19, and elevated activity of caspase-3 in contrast to non-treated cells. Levels of CYFRA 21-1 decreased significantly after caspase-3 was inhibited in TNF-alpha-treated cells. Thus, the release of CYFRA 21-1 may suggest cellular apoptosis in the process of tumor growth.