Monitoring autography in glioblastoma with antibody aganist isoform B of human microtuble-associated protein 1 light chain 3
Monitoring autography in glioblastoma with antibody aganist isoform B of human microtuble-associated protein 1 light chain 3
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DOI：
10.4161/auto.5668
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发表时间：
2008-05-16
期刊：
影响因子：
13.3
通讯作者：
Kondo, Seiji
中科院分区：
文献类型：
--
作者：
Aoki, Hiroshi;Kondo, Yasuko;Kondo, Seiji
自噬是一种进化上保守的应激反应，近年来被认为与癌症的发生和发展有关，但其具体机制和功能尚未完全阐明。我们理解的一个主要障碍是缺乏一种有效和强大的方法来特异性地监测癌症标本中的自噬细胞。为了鉴定与自噬相关的分子事件，我们对自噬性胶质母细胞瘤细胞系进行了cDNA微阵列分析。在此基础上，我们制备了抗人微管相关蛋白1轻链3（LC 3 B）亚型B的多克隆抗体。抗LC3B抗体的应用揭示了自噬细胞在体外和体内环境中的存在。在65例胶质母细胞瘤组织中，31例LC 3B在胞浆中呈高阳性表达。LC 3B细胞质染色与Karnofsky行为量表评分之间的统计学相互作用是显著的。LC3B的高表达与表现较差的患者的预后改善相关，而对于表现正常的患者，LC3B低染色的患者的生存率高于LC3B高染色的患者。抗LC3B抗体为监测癌细胞和组织中自噬的诱导提供了有用的工具。
Autophagy, an evolutionarily conserved response to stress, has recently been implicated in cancer initiation and progression, but the detailed mechanisms and functions have not yet been fully elucidated. One major obstacle to our understanding is lack of an efficient and robust method to specifically monitor autophagic cells in cancer specimens. To identify molecular events associated with autophagy, we performed cDNA microarray analysis of autophagic glioblastoma cell lines. Based on the analysis, we raised a polyclonal antibody against isoform B of human microtubule-associated protein 1 light chain 3 (LC3B). Application of the anti-LC3B antibody revealed the presence of autophagic cells in both in vitro and in vivo settings. Of the 65 glioblastoma tissues, 31 had highly positive cytoplasmic staining of LC3B. The statistical interaction between cytoplasmic staining of LC3B and Karnofsky Performance Scale score was significant. High expression of LC3B was associated with an improved outcome for patients with poorer performance, whereas' for patients with normal performance, survival was better for patients with low staining than with high staining of LC3B. Anti-LC3B antibody provides a useful tool for monitoring the induction of autophagy in cancer cells and tissues.