Monitoring autophagy in glioblastoma with antibody against isoform B of human microtubule-associated protein 1 light chain 3.
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.
Aoki
Hiroshi
H
Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
Kondo
Yasuko
Y
Aldape
Kenneth
K
Yamamoto
Akitsugu
A
Iwado
Eiji
E
Yokoyama
Tomohisa
T
Hollingsworth
E Faith
EF
Kobayashi
Ryuji
R
Hess
Kenneth
K
Shinojima
Naoki
N
Shingu
Takashi
T
Tamada
Yutaka
Y
Zhang
Li
L
Conrad
Charles
C
Bogler
Oliver
O
Mills
Gordon
G
Sawaya
Raymond
R
Kondo
Seiji
S
D000818:Animals; D000906:Antibodies / Q000276:immunology* / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000378:metabolism; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000378:metabolism; D001343:Autophagy / Q000502:physiology*; D045744:Cell Line, Tumor; D002518:Ceramides / Q000378:metabolism; D003606:Dacarbazine / Q000031:analogs & derivatives / Q000378:metabolism; D005260:Female; D005909:Glioblastoma / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D009368:Neoplasm Transplantation; D020411:Oligonucleotide Array Sequence Analysis; D010087:Oxides / Q000378:metabolism; D017239:Paclitaxel / Q000378:metabolism; D010588:Phagosomes / Q000378:metabolism / Q000648:ultrastructure; D015996:Survival Rate; D000077204:Temozolomide; D014183:Transplantation, Heterologous; D050257:Tubulin Modulators / Q000378:metabolism
D000906:Antibodies; D000970:Antineoplastic Agents; D001152:Arsenicals; D002518:Ceramides; C477012:MAP1LC3A protein, human; D008869:Microtubule-Associated Proteins; D010087:Oxides; D050257:Tubulin Modulators; D003606:Dacarbazine; D017239:Paclitaxel; D000077237:Arsenic Trioxide; D000077204:Temozolomide