Release of cytokeratin-18 and -19 fragments (TPS and CYFRA 21-1) into the extracellular space during apoptosis.

Abstract

Serum fragments of cytokeratins-18 and -19 (measured as TPS and CYFRA 21-1, respectively) have traditionally been considered as markers of tumor proliferation, although the evidence is scarce for a causative relationship between proliferation and levels of TPS and CYFRA 21-1. We examined whether apoptosis might produce TPS and CYFRA 21-1 fragments. MCF-7 breast cancer cells were treated with mitomycin C or agonistic anti-CD95 antibody, and levels of TPS and CYFRA 21-1 in tissue culture supernatants were compared with the frequency of cells exhibiting the following markers of cell death: intracellular cytokeratin-18 cleavage, surface staining with annexin-V, propidium iodide uptake, DNA fragmentation. Twenty-four hours after inducing apoptosis, levels of TPS and CYFRA 21-1 were elevated > or = 4-fold in culture supernatants. Elevations in TPS and CYFRA 21-1 coincided with apoptosis measured by the first three cell death markers but preceded DNA fragmentation. These mitomycin C- and CD95-mediated elevations were completely inhibited by co-incubation with the caspase inhibitors Z-VAD.fmk and Z-IETD.fmk, respectively. We conclude that TPS and CYFRA 21-1 can be abundantly released into the extracellular space during the intermediate stage of epithelial cell apoptosis.

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@article{Sheard2002ReleaseOC, title={Release of cytokeratin-18 and -19 fragments (TPS and CYFRA 21-1) into the extracellular space during apoptosis.}, author={Michael A Sheard and Borek Vojtesek and Marta Simickova and Dalibor Valik}, journal={Journal of cellular biochemistry}, year={2002}, volume={85 4}, pages={670-7} }