Monitoring autophagy in glioblastoma with antibody against isoform B of human microtubule-associated protein 1 light chain 3

Hiroshi Aoki, Yasuko Kondo, Kenneth Aldape, Akitsugu Yamamoto, Eiji Iwado, Tomohisa Yokoyama, E. Faith Hollingsworth, Ryuji Kobayashi, Kenneth Hess, Naoki Shinojima, Takashi Shingu, Yutaka Tamada, Li Zhang, Charles Conrad, Oliver Bogler, Gordon Mills, Raymond Sawaya, Seiji Kondo

Research output: Contribution to journalArticlepeer-review

113 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)467-475
Number of pages9
JournalAutophagy
Volume4
Issue number4
DOIs
StatePublished - May 16 2008
Externally publishedYes

Keywords

  • Apoptosis
  • Autophagy
  • Chemotherapy
  • Glioblastoma
  • LC3B

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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