Detection of epithelial cell death in the body by cytokeratin 18 measurement

Cell death is as important as cell division in both physiological and pathological processes. Three major types of cell death have been described: apoptosis, autophagy and necrosis. Apoptosis is a form of programmed cell death, mediated by caspases. Autophagy is an evolutionarily conserved process involving lysosomes, implicated in both cell survival and death. Necrosis is believed to be an unregulated process, followed by release of intracellular components. The epithelial-specific intermediate filament cytokeratin 18 (Kl8) has different fates depending on the type of cell death. During apoptosis, K18 is cleaved at two sites into three fragments, one of which is specifically recognized by the monoclonal antibody, M30. During autophagy K18 is reported to stay uncleaved. Necrotic cells are considered to release K18. Thus, serum levels of different forms of K18 would reflect the type of cell death occurring in the body. Two enzyme-linked immunosorbent assays have been developed: one for the cleaved fragments of K18 and the other for total K18. Detection of serum levels of cleaved and total K18 showed that the ratios between cleaved and total K18 were highly variable among patients with endometrial cancer. Monitoring serum levels of cleaved and total K18 during chemotherapy showed an association between increases in total K18 levels and clinical responses. Monitoring serum levels of K18 may be a promising approach for early detection of therapeutic effects and the levels of different forms of K18 might indicate the mode of cell death occurring in the body.