Monitoring autography in glioblastoma with antibody aganist isoform B of human microtuble-associated protein 1 light chain 3

被引:104
作者
Aoki, Hiroshi [1 ]
Kondo, Yasuko [1 ]
Aldape, Kenneth [2 ]
Yamamoto, Akitsugu [7 ]
Iwado, Eiji [1 ]
Yokoyama, Tomohisa [1 ]
Hollingsworth, E. Faith [1 ]
Kobayashi, Ryuji [3 ]
Hess, Kenneth [4 ]
Shinojima, Naoki [1 ]
Shingu, Takashi [1 ]
Tamada, Yutaka [1 ]
Zhang, Li [4 ]
Conrad, Charles [5 ]
Bogler, Oliver [1 ,8 ]
Mills, Gordon [6 ]
Sawaya, Raymond [1 ,8 ]
Kondo, Seiji [1 ,8 ,9 ]
机构
[1] Univ Texas MD Anderson Canc Ctr, Dept Neurosurg, Houston, TX 77030 USA
[2] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA
[3] Univ Texas MD Anderson Canc Ctr, Dept Mol Pathol, Houston, TX 77030 USA
[4] Univ Texas MD Anderson Canc Ctr, Dept Biostat & Appl Math, Houston, TX 77030 USA
[5] Univ Texas MD Anderson Canc Ctr, Dept Neurooncol, Houston, TX 77030 USA
[6] Univ Texas MD Anderson Canc Ctr, Dept Mol Therapeut, Houston, TX 77030 USA
[7] Nagahama Inst Biosci & Technol, Dept Cell Biol & Biosci, Shiga, Japan
[8] Baylor Coll Med, Dept Neurosurg, Houston, TX 77030 USA
[9] Univ Texas Houston, Grad Sch Biomed Sci, Program Mol Pathol, Houston, TX USA
关键词
autophagy; glioblastoma; LC3B; chemotherapy; apoptosis;
D O I
10.4161/auto.5668
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页码:467 / 475
页数:9
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