Ueno T, Toi M, Linder S
Cancer Center Karolinska, Department of Oncology-Pathology, Karolinska Institute and Hospital, Stockholm, Sweden.
Biomed Pharmacother. 2005 Oct;59 Suppl 2:S359-62. doi: 10.1016/s0753-3322(05)80078-2.
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.
细胞死亡在生理和病理过程中与细胞分裂同样重要。已描述了三种主要的细胞死亡类型：凋亡、自噬和坏死。凋亡是一种由半胱天冬酶介导的程序性细胞死亡形式。自噬是一个涉及溶酶体的进化保守过程，与细胞存活和死亡均有关。坏死被认为是一个不受调控的过程，随后会释放细胞内成分。上皮特异性中间丝细胞角蛋白18（K18）根据细胞死亡类型具有不同的命运。在凋亡过程中，K18在两个位点被切割成三个片段，其中一个片段可被单克隆抗体M30特异性识别。据报道，在自噬过程中K18保持未切割状态。坏死细胞被认为会释放K18。因此，不同形式K18的血清水平可反映体内发生的细胞死亡类型。已开发出两种酶联免疫吸附测定法：一种用于检测K18的切割片段，另一种用于检测总K18。对子宫内膜癌患者血清中切割型和总K18水平的检测表明，切割型与总K18的比率在患者中差异很大。化疗期间监测血清中切割型和总K18水平显示，总K18水平升高与临床反应之间存在关联。监测血清K18水平可能是早期检测治疗效果的一种有前景的方法，并且不同形式K18的水平可能表明体内发生的细胞死亡模式。
