Full-length cytokeratin 8 is released and circulates in patients with non-small cell lung cancer
Full-length cytokeratin 8 is released and circulates in patients with non-small cell lung cancer
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DOI：
10.1159/000132572
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发表时间：
2008-01-01
期刊：
影响因子：
--
通讯作者：
Kubo, Akihito
中科院分区：
文献类型：
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作者：
Ishii, Tomoya;Bandoh, Shuji;Kubo, Akihito
背景/目的：细胞角蛋白8(CK8)是一种II型中间丝蛋白，在大多数上皮性恶性肿瘤中持续表达。循环CK相关多肽通常被用作肿瘤标记物。虽然细胞凋亡是CK释放的一种机制，但人们对循环CKs的分子本质知之甚少。目的是为了阐明CK8在体外细胞凋亡过程中的动态变化以及肺癌患者循环中CK8的性质。方法：用依托泊苷诱导人非小细胞肺癌(NSCLC)A549细胞凋亡，检测细胞外CK8的释放。采用酶联免疫吸附试验(EL ISA)和免疫沉淀法分别检测60例非小细胞肺癌患者和9例非小细胞肺癌患者血清循环CK8。结果：与I型CK18不同，A549细胞在凋亡过程中CK8主要被全长释放，并能抵抗caspase的胞内切割。全长CK8在肺癌患者血清中占循环CK8的相当大一部分。结论：细胞凋亡导致NSCLC细胞外释放全长CK8。CK8在NSCLC患者中主要以全长循环，说明了I型和II型CKS在蛋白质加工方面的根本差异。版权所有(C)2008 S.Karger AG，巴塞尔。
Background/Aim: Cytokeratin 8 (CK8) is a type II intermediate filament protein that is persistently expressed in most epithelial malignancies. Circulating CK-related polypeptides have commonly been used as tumor markers. While apoptosis is a mechanism of CK release, the molecular nature of circulating CKs is poorly understood. The aim is to clarify the dynamics of CK8 during apoptosis in vitro and the nature of circulating CK8 in patients with lung cancer. Methods: Extracellular release of CK8 was examined using A549 human non-small cell lung cancer (NSCLC) cells after apoptosis induction by etoposide. Serum samples from NSCLC patients were examined for circulating CK8 by ELISA (n = 60) and by immunoprecipitation (n = 9). Results: CK8 is released predominantly in full length from A549 cells undergoing apoptosis and is resistant to intracellular cleavage by caspases, unlike type I CK18, which is readily cleaved during apoptosis. Full-length CK8 is shown to constitute a considerable fraction of circulating CK8 in the serum of lung cancer patients. Conclusion: Apoptosis causes extracellular release of full-length CK8 in NSCLC cells. CK8 circulates predominantly in full length in patients with NSCLC, illustrating the fundamental differences in protein processing between type I and type II CKs. Copyright (C) 2008 S. Karger AG, Basel.