CYFRA 21-1 is released in TNF-alpha-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.
Third Department of Internal Medicine, Kagawa Medical University, Kagawa, Japan.
Fei
F
Wu
Jiro
J
Fujita
Masayuki
M
Murota
Jia-Qing
JQ
Li
Toshihiko
T
Ishida
Mikio
M
Nishioka
Yuji
Y
Imaida
Shigeki
S
Kuriyama
D000951:Antigens, Neoplasm / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D014408:Biomarkers, Tumor; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D003470:Culture Media; D006801:Humans; D007124:Immunoenzyme Techniques; D053539:Keratin-19; D007633:Keratins; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D003470:Culture Media; D053539:Keratin-19; D014409:Tumor Necrosis Factor-alpha; C102012:antigen CYFRA21.1; D007633:Keratins; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases