Aoki Hiroshi, Kondo Yasuko, Aldape Kenneth, Yamamoto Akitsugu, Iwado Eiji, Yokoyama Tomohisa, Hollingsworth E Faith, Kobayashi Ryuji, Hess Kenneth, Shinojima Naoki, Shingu Takashi, Tamada Yutaka, Zhang Li, Conrad Charles, Bogler Oliver, Mills Gordon, Sawaya Raymond, Kondo Seiji
Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
Autophagy. 2008 May;4(4):467-75. doi: 10.4161/auto.5668. Epub 2008 Feb 4.
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.
自噬是一种进化上保守的应激反应,最近被认为与癌症的发生和发展有关,但其详细机制和功能尚未完全阐明。我们理解这一过程的一个主要障碍是缺乏一种有效且可靠的方法来特异性监测癌症标本中的自噬细胞。为了识别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。基于该分析,我们制备了一种针对人微管相关蛋白1轻链3(LC3B)异构体B的多克隆抗体。抗LC3B抗体的应用揭示了在体外和体内环境中均存在自噬细胞。在65个胶质母细胞瘤组织中,31个组织的LC3B胞质染色呈强阳性。LC3B胞质染色与卡氏功能状态评分之间的统计学交互作用显著。LC3B的高表达与表现较差的患者预后改善相关,而对于表现正常的患者,LC3B低染色患者的生存率高于高染色患者。抗LC3B抗体为监测癌细胞和组织中自噬的诱导提供了一种有用的工具。